Iron is a biochemically critical metal cofactor in enzymes involved in photosynthesis, cellular respiration, nitrate assimilation, nitrogen fixation, and reactive oxygen species defense. Marine microeukaryotes have evolved a phytotransferrin-based iron uptake system to cope with iron scarcity, a major factor limiting primary productivity in the global ocean. Diatom phytotransferrin is endocytosed; however, proteins downstream of this environmentally ubiquitous iron receptor are unknown. We applied engineered ascorbate peroxidase APEX2-based subcellular proteomics to catalog proximal proteins of phytotransferrin in the model marine diatom Phaeodactylum tricornutum. Proteins encoded by poorly characterized iron-sensitive genes were identified including three that are expressed from a chromosomal gene cluster. Two of them showed unambiguous colocalization with phytotransferrin adjacent to the chloroplast. Further phylogenetic, domain, and biochemical analyses suggest their involvement in intracellular iron processing. Proximity proteomics holds enormous potential to glean new insights into iron acquisition pathways and beyond in these evolutionarily, ecologically, and biotechnologically important microalgae.

Biological and Biomedical Sciences The Graduate School of Arts and Sciences Harvard University Cambridge United States

Biology Centre CAS Institute of Parasitology České Budějovice Czech Republic

Center for Marine Biotechnology and Biomedicine Scripps Institution of Oceanography University of California San Diego La Jolla United States

Center for Research in Biological Systems University of California San Diego La Jolla United States

Department of Systems Biology Harvard Medical School Boston United States

Informatics J Craig Venter Institute La Jolla United States

Integrative Oceanography Division Scripps Institution of Oceanography University of California San Diego La Jolla United States

Microbial and Environmental Genomics J Craig Venter Institute La Jolla United States

National Center for Microscopy and Imaging Research University of California San Diego La Jolla United States

Synthetic Biology and Bioenergy J Craig Venter Institute La Jolla United States

University of South Bohemia Faculty of Science České Budějovice Czech Republic

Wyss Institute for Biologically Inspired Engineering Harvard University Boston United States

Zobrazit více v PubMed

Aguirre JD, Clark HM, McIlvin M, Vazquez C, Palmere SL, Grab DJ, Seshu J, Hart PJ, Saito M, Culotta VC. A manganese-rich environment supports superoxide dismutase activity in a lyme disease pathogen, Borrelia burgdorferi. Journal of Biological Chemistry. 2013;288:8468–8478. doi: 10.1074/jbc.M112.433540. PubMed DOI PMC

Allen AE, Laroche J, Maheswari U, Lommer M, Schauer N, Lopez PJ, Finazzi G, Fernie AR, Bowler C. Whole-cell response of the pennate diatom Phaeodactylum tricornutum to iron starvation. PNAS. 2008;105:10438–10443. doi: 10.1073/pnas.0711370105. PubMed DOI PMC

Allen AE, Moustafa A, Montsant A, Eckert A, Kroth PG, Bowler C. Evolution and functional diversification of fructose bisphosphate aldolase genes in photosynthetic marine diatoms. Molecular Biology and Evolution. 2012;29:367–379. doi: 10.1093/molbev/msr223. PubMed DOI PMC

Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. Journal of Molecular Biology. 1990;215:403–410. doi: 10.1016/S0022-2836(05)80360-2. PubMed DOI

Archibald JM. The puzzle of plastid evolution. Current Biology. 2009;19:R81–R88. doi: 10.1016/j.cub.2008.11.067. PubMed DOI

Ardyna M, Lacour L, Sergi S, d'Ovidio F, Sallée JB, Rembauville M, Blain S, Tagliabue A, Schlitzer R, Jeandel C, Arrigo KR, Claustre H. Hydrothermal vents trigger massive phytoplankton blooms in the southern ocean. Nature Communications. 2019;10:2451. doi: 10.1038/s41467-019-09973-6. PubMed DOI PMC

Aron AT, Ramos-Torres KM, Cotruvo JA, Chang CJ. Recognition- and reactivity-based fluorescent probes for studying transition metal signaling in living systems. Accounts of Chemical Research. 2015;48:2434–2442. doi: 10.1021/acs.accounts.5b00221. PubMed DOI PMC

Balk J, Schaedler TA. Iron cofactor assembly in plants. Annual Review of Plant Biology. 2014;65:125–153. doi: 10.1146/annurev-arplant-050213-035759. PubMed DOI

Banci L, Bertini I, Ciofi-Baffoni S, Finney LA, Outten CE, O'Halloran TV. A new zinc-protein coordination site in intracellular metal trafficking: solution structure of the apo and zn(II) forms of ZntA(46-118) Journal of Molecular Biology. 2002;323:883–897. doi: 10.1016/S0022-2836(02)01007-0. PubMed DOI

Banci L, Bertini I, Ciofi-Baffoni S, Su XC, Miras R, Bal N, Mintz E, Catty P, Shokes JE, Scott RA. Structural basis for metal binding specificity: the N-terminal cadmium binding domain of the P1-type ATPase CadA. Journal of Molecular Biology. 2006;356:638–650. doi: 10.1016/j.jmb.2005.11.055. PubMed DOI PMC

Bard F, Chia J. Cracking the glycome encoder: signaling, trafficking, and glycosylation. Trends in Cell Biology. 2016;26:379–388. doi: 10.1016/j.tcb.2015.12.004. PubMed DOI

Barrett J, Girr P, Mackinder LCM. Pyrenoids: CO2-fixing phase separated liquid organelles. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research. 2021;1868:118949. doi: 10.1016/j.bbamcr.2021.118949. PubMed DOI

Baslam M, Oikawa K, Kitajima-Koga A, Kaneko K, Mitsui T. Golgi-to-plastid trafficking of proteins through secretory pathway: insights into vesicle-mediated import toward the plastids. Plant Signaling & Behavior. 2016;11:e1221558. doi: 10.1080/15592324.2016.1221558. PubMed DOI PMC

Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP. A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature Biotechnology. 2006;24:1285–1292. doi: 10.1038/nbt1240. PubMed DOI

Behnke J, LaRoche J. Iron uptake proteins in algae and the role of iron Starvation-Induced proteins (ISIPs) European Journal of Phycology. 2020;55:339–360. doi: 10.1080/09670262.2020.1744039. DOI

Benham AM. Protein secretion and the endoplasmic reticulum. Cold Spring Harbor Perspectives in Biology. 2012;4:a012872. doi: 10.1101/cshperspect.a012872. PubMed DOI PMC

Benoiston AS, Ibarbalz FM, Bittner L, Guidi L, Jahn O, Dutkiewicz S, Bowler C. The evolution of diatoms and their biogeochemical functions. Philosophical Transactions of the Royal Society B: Biological Sciences. 2017;372:20160397. doi: 10.1098/rstb.2016.0397. PubMed DOI PMC

Bertrand EM, McCrow JP, Moustafa A, Zheng H, McQuaid JB, Delmont TO, Post AF, Sipler RE, Spackeen JL, Xu K, Bronk DA, Hutchins DA, Allen AE. Phytoplankton-bacterial interactions mediate micronutrient colimitation at the coastal antarctic sea ice edge. PNAS. 2015;112:9938–9943. doi: 10.1073/pnas.1501615112. PubMed DOI PMC

Bhaya D, Grossman AR. Characterization of gene clusters encoding the fucoxanthin chlorophyll proteins of the diatom Phaeodactylum tricornutum. Nucleic Acids Research. 1993;21:4458–4466. doi: 10.1093/nar/21.19.4458. PubMed DOI PMC

Blaby-Haas CE, Padilla-Benavides T, Stübe R, Argüello JM, Merchant SS. Evolution of a plant-specific copper chaperone family for chloroplast copper homeostasis. PNAS. 2014;111:E5480–E5487. doi: 10.1073/pnas.1421545111. PubMed DOI PMC

Blaby-Haas CE, Merchant SS. The ins and outs of algal metal transport. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research. 2012;1823:1531–1552. doi: 10.1016/j.bbamcr.2012.04.010. PubMed DOI PMC

Blaby-Haas CE, Merchant SS. Lysosome-related organelles as mediators of metal homeostasis. Journal of Biological Chemistry. 2014;289:28129–28136. doi: 10.1074/jbc.R114.592618. PubMed DOI PMC

Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends in Biochemical Sciences. 2016;41:274–286. doi: 10.1016/j.tibs.2015.11.012. PubMed DOI PMC

Boiteau RM, Mende DR, Hawco NJ, McIlvin MR, Fitzsimmons JN, Saito MA, Sedwick PN, DeLong EF, Repeta DJ. Siderophore-based microbial adaptations to iron scarcity across the eastern pacific ocean. PNAS. 2016;113:14237–14242. doi: 10.1073/pnas.1608594113. PubMed DOI PMC

Bonfio C, Valer L, Scintilla S, Shah S, Evans DJ, Jin L, Szostak JW, Sasselov DD, Sutherland JD, Mansy SS. UV-light-driven prebiotic synthesis of iron-sulfur clusters. Nature Chemistry. 2017;9:1229–1234. doi: 10.1038/nchem.2817. PubMed DOI PMC

Boukouris AE, Zervopoulos SD, Michelakis ED. Metabolic enzymes moonlighting in the nucleus: metabolic regulation of gene transcription. Trends in Biochemical Sciences. 2016;41:712–730. doi: 10.1016/j.tibs.2016.05.013. PubMed DOI

Bowler C, Allen AE, Badger JH, Grimwood J, Jabbari K, Kuo A, Maheswari U, Martens C, Maumus F, Otillar RP, Rayko E, Salamov A, Vandepoele K, Beszteri B, Gruber A, Heijde M, Katinka M, Mock T, Valentin K, Verret F, Berges JA, Brownlee C, Cadoret JP, Chiovitti A, Choi CJ, Coesel S, De Martino A, Detter JC, Durkin C, Falciatore A, Fournet J, Haruta M, Huysman MJ, Jenkins BD, Jiroutova K, Jorgensen RE, Joubert Y, Kaplan A, Kröger N, Kroth PG, La Roche J, Lindquist E, Lommer M, Martin-Jézéquel V, Lopez PJ, Lucas S, Mangogna M, McGinnis K, Medlin LK, Montsant A, Oudot-Le Secq MP, Napoli C, Obornik M, Parker MS, Petit JL, Porcel BM, Poulsen N, Robison M, Rychlewski L, Rynearson TA, Schmutz J, Shapiro H, Siaut M, Stanley M, Sussman MR, Taylor AR, Vardi A, von Dassow P, Vyverman W, Willis A, Wyrwicz LS, Rokhsar DS, Weissenbach J, Armbrust EV, Green BR, Van de Peer Y, Grigoriev IV. The Phaeodactylum genome reveals the evolutionary history of diatom genomes. Nature. 2008;456:239–244. doi: 10.1038/nature07410. PubMed DOI

Branon TC, Bosch JA, Sanchez AD, Udeshi ND, Svinkina T, Carr SA, Feldman JL, Perrimon N, Ting AY. Efficient proximity labeling in living cells and organisms with TurboID. Nature Biotechnology. 2018;36:880–887. doi: 10.1038/nbt.4201. PubMed DOI PMC

Brenner MP. Endocytic traffic: vesicle fusion cascade in the early endosomes. Current Biology. 2012;22:R597–R598. doi: 10.1016/j.cub.2012.06.009. PubMed DOI

Brunson JK, McKinnie SMK, Chekan JR, McCrow JP, Miles ZD, Bertrand EM, Bielinski VA, Luhavaya H, Oborník M, Smith GJ, Hutchins DA, Allen AE, Moore BS. Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom. Science. 2018;361:1356–1358. doi: 10.1126/science.aau0382. PubMed DOI PMC

Brzezinski MA, Krause JW, Bundy RM, Barbeau KA, Franks P, Goericke R, Landry MR, Stukel MR. Enhanced silica ballasting from iron stress sustains carbon export in a frontal zone within the California current. Journal of Geophysical Research: Oceans. 2015;120:4654–4669. doi: 10.1002/2015JC010829. DOI

Camacho A, Walter XA, Picazo A, Zopfi J. Photoferrotrophy: remains of an ancient photosynthesis in modern environments. Frontiers in Microbiology. 2017;8:323. doi: 10.3389/fmicb.2017.00323. PubMed DOI PMC

Cao H, Schroeder B, Chen J, Schott MB, McNiven MA. The endocytic fate of the transferrin receptor is regulated by c-Abl kinase. Journal of Biological Chemistry. 2016;291:16424–16437. doi: 10.1074/jbc.M116.724997. PubMed DOI PMC

Caron DA, Alexander H, Allen AE, Archibald JM, Armbrust EV, Bachy C, Bell CJ, Bharti A, Dyhrman ST, Guida SM, Heidelberg KB, Kaye JZ, Metzner J, Smith SR, Worden AZ. Probing the evolution, ecology and physiology of marine protists using transcriptomics. Nature Reviews Microbiology. 2017;15:6–20. doi: 10.1038/nrmicro.2016.160. PubMed DOI

Cheng Y, Zak O, Aisen P, Harrison SC, Walz T. Structure of the human transferrin receptor-transferrin complex. Cell. 2004;116:565–576. doi: 10.1016/S0092-8674(04)00130-8. PubMed DOI

Cieśla M, Mierzejewska J, Adamczyk M, Farrants AK, Boguta M. Fructose bisphosphate aldolase is involved in the control of RNA polymerase III-directed transcription. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research. 2014;1843:1103–1110. doi: 10.1016/j.bbamcr.2014.02.007. PubMed DOI

Coale TH, Moosburner M, Horák A, Oborník M, Barbeau KA, Allen AE. Reduction-dependent siderophore assimilation in a model pennate diatom. PNAS. 2019;116:23609–23617. doi: 10.1073/pnas.1907234116. PubMed DOI PMC

Cohen NR, Ellis KA, Burns WG, Lampe RH, Schuback N, Johnson Z, Sañudo-Wilhelmy S, Marchetti A. Iron and vitamin interactions in marine diatom isolates and natural assemblages of the northeast pacific ocean: iron and vitamin interactions in diatoms. Limnology and Oceanography. 2017a;62:2076–2096. doi: 10.1002/lno.10552. DOI

Cohen NR, Ellis KA, Lampe RH, McNair H, Twining BS, Maldonado MT, Brzezinski MA, Kuzminov FI, Thamatrakoln K, Till CP, Bruland KW, Sunda WG, Bargu S, Marchetti A. Diatom transcriptional and physiological responses to changes in iron bioavailability across ocean provinces. Frontiers in Marine Science. 2017b;4:360. doi: 10.3389/fmars.2017.00360. DOI

Cohen NR, Gong W, Moran DM, McIlvin MR, Saito MA, Marchetti A. Transcriptomic and proteomic responses of the oceanic diatom Pseudo-nitzschia granii to iron limitation. Environmental Microbiology. 2018;20:3109–3126. doi: 10.1111/1462-2920.14386. PubMed DOI

Coves J, Fontecave M. Reduction and mobilization of iron by a NAD(P)H:flavin oxidoreductase from Escherichia coli. European Journal of Biochemistry. 1993;211:635–641. doi: 10.1111/j.1432-1033.1993.tb17591.x. PubMed DOI

Crichton R. Iron Metabolism: From Molecular Mechanisms to Clinical Consequences. Hoboken, NJ, USA: John Wiley & Sons, Inc; 2016. DOI

de Baar HJW. Synthesis of iron fertilization experiments: from the iron age in the age of enlightenment. Journal of Geophysical Research. 2005;110:C09S16. doi: 10.1029/2004JC002601. DOI

Del Olmo T, Lauzier A, Normandin C, Larcher R, Lecours M, Jean D, Lessard L, Steinberg F, Boisvert FM, Jean S. APEX2-mediated RAB proximity labeling identifies a role for RAB21 in clathrin-independent cargo sorting. EMBO Reports. 2019;20:e47192. doi: 10.15252/embr.201847192. PubMed DOI PMC

Di Bacco A, Gill G. The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor II receptor. Oncogene. 2003;22:5436–5445. doi: 10.1038/sj.onc.1206670. PubMed DOI

Diner RE, Bielinski VA, Dupont CL, Allen AE, Weyman PD. Refinement of the diatom episome maintenance sequence and improvement of Conjugation-Based DNA delivery methods. Frontiers in Bioengineering and Biotechnology. 2016;4:65. doi: 10.3389/fbioe.2016.00065. PubMed DOI PMC

Diner RE, Noddings CM, Lian NC, Kang AK, McQuaid JB, Jablanovic J, Espinoza JL, Nguyen NA, Anzelmatti MA, Jansson J, Bielinski VA, Karas BJ, Dupont CL, Allen AE, Weyman PD. Diatom centromeres suggest a mechanism for nuclear DNA acquisition. PNAS. 2017;114:E6015–E6024. doi: 10.1073/pnas.1700764114. PubMed DOI PMC

Dokmanić I, Sikić M, Tomić S. Metals in proteins: correlation between the metal-ion type, coordination number and the amino-acid residues involved in the coordination. Acta Crystallographica Section D Biological Crystallography. 2008;64:257–263. doi: 10.1107/S090744490706595X. PubMed DOI

Durkin CA, Marchetti A, Bender SJ, Truong T, Morales R, Mock T, Armbrust EV. Frustule-related gene transcription and the influence of diatom community composition on silica precipitation in an iron-limited environment. Limnology and Oceanography. 2012;57:1619–1633. doi: 10.4319/lo.2012.57.6.1619. DOI

Eckenroth BE, Steere AN, Chasteen ND, Everse SJ, Mason AB. How the binding of human transferrin primes the transferrin receptor potentiating iron release at endosomal pH. PNAS. 2011;108:13089–13094. doi: 10.1073/pnas.1105786108. PubMed DOI PMC

Eddy SR. Profile hidden markov models. Bioinformatics. 1998;14:755–763. doi: 10.1093/bioinformatics/14.9.755. PubMed DOI

El-Gebali S, Mistry J, Bateman A, Eddy SR, Luciani A, Potter SC, Qureshi M, Richardson LJ, Salazar GA, Smart A, Sonnhammer ELL, Hirsh L, Paladin L, Piovesan D, Tosatto SCE, Finn RD. The pfam protein families database in 2019. Nucleic Acids Research. 2019;47:D427–D432. doi: 10.1093/nar/gky995. PubMed DOI PMC

Emanuelsson O, Nielsen H, Brunak S, von Heijne G. Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. Journal of Molecular Biology. 2000;300:1005–1016. doi: 10.1006/jmbi.2000.3903. PubMed DOI

Eng JK, McCormack AL, Yates JR. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. Journal of the American Society for Mass Spectrometry. 1994;5:976–989. doi: 10.1016/1044-0305(94)80016-2. PubMed DOI

Faktorová D, Nisbet RER, Fernández Robledo JA, Casacuberta E, Sudek L, Allen AE, Ares M, Aresté C, Balestreri C, Barbrook AC, Beardslee P, Bender S, Booth DS, Bouget FY, Bowler C, Breglia SA, Brownlee C, Burger G, Cerutti H, Cesaroni R, Chiurillo MA, Clemente T, Coles DB, Collier JL, Cooney EC, Coyne K, Docampo R, Dupont CL, Edgcomb V, Einarsson E, Elustondo PA, Federici F, Freire-Beneitez V, Freyria NJ, Fukuda K, García PA, Girguis PR, Gomaa F, Gornik SG, Guo J, Hampl V, Hanawa Y, Haro-Contreras ER, Hehenberger E, Highfield A, Hirakawa Y, Hopes A, Howe CJ, Hu I, Ibañez J, Irwin NAT, Ishii Y, Janowicz NE, Jones AC, Kachale A, Fujimura-Kamada K, Kaur B, Kaye JZ, Kazana E, Keeling PJ, King N, Klobutcher LA, Lander N, Lassadi I, Li Z, Lin S, Lozano JC, Luan F, Maruyama S, Matute T, Miceli C, Minagawa J, Moosburner M, Najle SR, Nanjappa D, Nimmo IC, Noble L, Novák Vanclová AMG, Nowacki M, Nuñez I, Pain A, Piersanti A, Pucciarelli S, Pyrih J, Rest JS, Rius M, Robertson D, Ruaud A, Ruiz-Trillo I, Sigg MA, Silver PA, Slamovits CH, Jason Smith G, Sprecher BN, Stern R, Swart EC, Tsaousis AD, Tsypin L, Turkewitz A, Turnšek J, Valach M, Vergé V, von Dassow P, von der Haar T, Waller RF, Wang L, Wen X, Wheeler G, Woods A, Zhang H, Mock T, Worden AZ, Lukeš J. Genetic tool development in marine protists: emerging model organisms for experimental cell biology. Nature Methods. 2020;17:481–494. doi: 10.1038/s41592-020-0796-x. PubMed DOI PMC

Falciatore A, Jaubert M, Bouly JP, Bailleul B, Mock T. Diatom molecular research comes of age: model species for studying phytoplankton biology and diversity. The Plant Cell. 2020;32:547–572. doi: 10.1105/tpc.19.00158. PubMed DOI PMC

Finbow ME, Harrison MA. The vacuolar H+-ATPase: a universal proton pump of eukaryotes. Biochemical Journal. 1997;324 (Pt 3):697–712. doi: 10.1042/bj3240697. PubMed DOI PMC

Fomenko DE, Marino SM, Gladyshev VN. Functional diversity of cysteine residues in proteins and unique features of catalytic Redox-Active cysteines in thiol oxidoreductases. Molecules and Cells. 2008;26:228–235. PubMed PMC

Fomenko DE, Gladyshev VN. Identity and functions of CxxC-derived motifs. Biochemistry. 2003;42:11214–11225. doi: 10.1021/bi034459s. PubMed DOI

Francius G, Tesson B, Dague E, Martin-Jézéquel V, Dufrêne YF. Nanostructure and nanomechanics of live Phaeodactylum tricornutum morphotypes. Environmental Microbiology. 2008;10:1344–1356. doi: 10.1111/j.1462-2920.2007.01551.x. PubMed DOI

Füssy Z, Oborník M. Complex Endosymbioses I: From Primary to Complex Plastids, Multiple IndependentEvents. In: Maréchal E, editor. Plastids. Methods in Molecular Biology. Vol. 1829. Totowa, United States: Humana Press, Inc; 2018. pp. 17–35. PubMed DOI

Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A. Protein Identification and Analysis Tools on the ExPASy Server. In: Walker JM, editor. The Proteomics Protocols Handbook. Totowa, United States: Humana Press, Inc; 2005. pp. 571–607. DOI

Ghobrial G, Araujo L, Jinwala F, Li S, Lee LY. The structure and biological function of CREG. Frontiers in Cell and Developmental Biology. 2018;6:136. doi: 10.3389/fcell.2018.00136. PubMed DOI PMC

Ghosh P, Dahms NM, Kornfeld S. Mannose 6-phosphate receptors: new twists in the tale. Nature Reviews Molecular Cell Biology. 2003;4:202–213. doi: 10.1038/nrm1050. PubMed DOI

Gibbs SP. The Chloroplast Endoplasmic Reticulum: Structure, Function, and Evolutionary Significance. In: Bourne G. H, Danielli J. F, Jeon K. W, editors. International Review of Cytology. New York, United States: Academic Press, Inc; 1981. pp. 49–99. DOI

Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, Smith HO. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nature Methods. 2009;6:343–345. doi: 10.1038/nmeth.1318. PubMed DOI

Gingras AC, Abe KT, Raught B. Getting to know the neighborhood: using proximity-dependent biotinylation to characterize protein complexes and map organelles. Current Opinion in Chemical Biology. 2019;48:44–54. doi: 10.1016/j.cbpa.2018.10.017. PubMed DOI

Gizak A, Wiśniewski J, Heron P, Mamczur P, Sygusch J, Rakus D. Targeting a moonlighting function of aldolase induces apoptosis in Cancer cells. Cell Death & Disease. 2019;10:712. doi: 10.1038/s41419-019-1968-4. PubMed DOI PMC

Gladyshev VN, Kryukov GV, Fomenko DE, Hatfield DL. Identification of trace element-containing proteins in genomic databases. Annual Review of Nutrition. 2004;24:579–596. doi: 10.1146/annurev.nutr.24.012003.132241. PubMed DOI

Gouy M, Guindon S, Gascuel O. SeaView version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Molecular Biology and Evolution. 2010;27:221–224. doi: 10.1093/molbev/msp259. PubMed DOI

Grant CR, Komeili A. Ferrosomes are iron storage organelles formed by broadly conserved gene clusters in bacteria and archaea. bioRxiv. 2020 doi: 10.1101/2020.01.10.902569. DOI

Gröger P, Poulsen N, Klemm J, Kröger N, Schlierf M. Establishing super-resolution imaging for proteins in diatom biosilica. Scientific Reports. 2016;6:36824. doi: 10.1038/srep36824. PubMed DOI PMC

Grosche C, Hempel F, Bolte K, Zauner S, Maier UG. The periplastidal compartment: a naturally minimized eukaryotic cytoplasm. Current Opinion in Microbiology. 2014;22:88–93. doi: 10.1016/j.mib.2014.09.017. PubMed DOI

Gruber A, Rocap G, Kroth PG, Armbrust EV, Mock T. Plastid proteome prediction for diatoms and other algae with secondary plastids of the red lineage. The Plant Journal. 2015;81:519–528. doi: 10.1111/tpj.12734. PubMed DOI PMC

Gupta R, Jung E, Brunak S. Prediction of N-glycosylation sites in human proteins. [October 2, 2020];2004 https://services.healthtech.dtu.dk/service.php?NetNGlyc-1.0

Hamdi A, Roshan TM, Kahawita TM, Mason AB, Sheftel AD, Ponka P. Erythroid cell mitochondria receive endosomal iron by a "kiss-and-run" mechanism. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research. 2016;1863:2859–2867. doi: 10.1016/j.bbamcr.2016.09.008. PubMed DOI

Han Y, Cui J, Tao J, Guo L, Guo P, Sun M, Kang J, Zhang X, Yan C, Li S. CREG inhibits migration of human vascular smooth muscle cells by mediating IGF-II endocytosis. Experimental Cell Research. 2009;315:3301–3311. doi: 10.1016/j.yexcr.2009.09.013. PubMed DOI

Han Y, Luan B, Sun M, Guo L, Guo P, Tao J, Deng J, Wu G, Liu S, Yan C, Li S. Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic modulation of vascular smooth muscle cells. Journal of Molecular and Cellular Cardiology. 2011;50:723–730. doi: 10.1016/j.yjmcc.2010.12.013. PubMed DOI

Hertle AP, García-Cerdán JG, Armbruster U, Shih R, Lee JJ, Wong W, Niyogi KK. A Sec14 domain protein is required for photoautotrophic growth and chloroplast vesicle formation in Arabidopsis thaliana. PNAS. 2020;117:9101–9111. doi: 10.1073/pnas.1916946117. PubMed DOI PMC

Hildebrand M, Lerch SJL, Shrestha RP. Understanding diatom cell wall Silicification—Moving Forward. Frontiers in Marine Science. 2018;5:125. doi: 10.3389/fmars.2018.00125. DOI

Hogle SL, Barbeau KA, Gledhill M. Heme in the marine environment: from cells to the iron cycle. Metallomics. 2014;6:1107–1120. doi: 10.1039/C4MT00031E. PubMed DOI

Hong-Hermesdorf A, Miethke M, Gallaher SD, Kropat J, Dodani SC, Chan J, Barupala D, Domaille DW, Shirasaki DI, Loo JA, Weber PK, Pett-Ridge J, Stemmler TL, Chang CJ, Merchant SS. Subcellular metal imaging identifies dynamic sites of cu accumulation in Chlamydomonas. Nature Chemical Biology. 2014;10:1034–1042. doi: 10.1038/nchembio.1662. PubMed DOI PMC

Hung V, Udeshi ND, Lam SS, Loh KH, Cox KJ, Pedram K, Carr SA, Ting AY. Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. Nature Protocols. 2016;11:456–475. doi: 10.1038/nprot.2016.018. PubMed DOI PMC

Hutchins DA, Boyd PW. Marine phytoplankton and the changing ocean iron cycle. Nature Climate Change. 2016;6:1072–1079. doi: 10.1038/nclimate3147. DOI

Hutchins DA, Bruland KW. Iron-limited diatom growth and si:n uptake ratios in a coastal upwelling regime. Nature. 1998;393:561–564. doi: 10.1038/31203. DOI

Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villén J, Haas W, Sowa ME, Gygi SP. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010;143:1174–1189. doi: 10.1016/j.cell.2010.12.001. PubMed DOI PMC

Huysman MJ, Vyverman W, De Veylder L. Molecular regulation of the diatom cell cycle. Journal of Experimental Botany. 2014;65:2573–2584. doi: 10.1093/jxb/ert387. PubMed DOI

Hwang J, Ribbens D, Raychaudhuri S, Cairns L, Gu H, Frost A, Urban S, Espenshade PJ. A Golgi rhomboid protease Rbd2 recruits Cdc48 to cleave yeast SREBP. The EMBO Journal. 2016;35:2332–2349. doi: 10.15252/embj.201693923. PubMed DOI PMC

Hwang J, Espenshade PJ. Proximity-dependent biotin labelling in yeast using the engineered ascorbate peroxidase APEX2. Biochemical Journal. 2016;473:2463–2469. doi: 10.1042/BCJ20160106. PubMed DOI PMC

Jeffery CJ. Protein moonlighting: what is it, and why is it important? Philosophical Transactions of the Royal Society B: Biological Sciences. 2018;373:20160523. doi: 10.1098/rstb.2016.0523. PubMed DOI PMC

Jensen EC. Use of fluorescent probes: their effect on cell biology and limitations. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology. 2012;295:2031–2036. doi: 10.1002/ar.22602. PubMed DOI

Jeong J, Cohu C, Kerkeb L, Pilon M, Connolly EL, Guerinot ML. Chloroplast Fe(III) chelate reductase activity is essential for seedling viability under iron limiting conditions. PNAS. 2008;105:10619–10624. doi: 10.1073/pnas.0708367105. PubMed DOI PMC

Jin L, Engelhart AE, Zhang W, Adamala K, Szostak JW. Catalysis of Template-Directed nonenzymatic RNA copying by iron(II) Journal of the American Chemical Society. 2018;140:15016–15021. doi: 10.1021/jacs.8b09617. PubMed DOI PMC

Kalocsay M. APEX Peroxidase-Catalyzed Proximity Labeling and Multiplexed Quantitative Proteomics. In: Sunbul M, Jäschke A, editors. Proximity Labeling. TotawaUnited States: Human Press, Inc; 2019. pp. 41–55. PubMed DOI

Karas BJ, Diner RE, Lefebvre SC, McQuaid J, Phillips AP, Noddings CM, Brunson JK, Valas RE, Deerinck TJ, Jablanovic J, Gillard JT, Beeri K, Ellisman MH, Glass JI, Hutchison CA, Smith HO, Venter JC, Allen AE, Dupont CL, Weyman PD. Designer diatom episomes delivered by bacterial conjugation. Nature Communications. 2015;6:6925. doi: 10.1038/ncomms7925. PubMed DOI PMC

Katoh K, Misawa K, Kuma K, Miyata T. MAFFT: a novel method for rapid multiple sequence alignment based on fast fourier transform. Nucleic Acids Research. 2002;30:3059–3066. doi: 10.1093/nar/gkf436. PubMed DOI PMC

Kazamia E, Sutak R, Paz-Yepes J, Dorrell RG, Vieira FRJ, Mach J, Morrissey J, Leon S, Lam F, Pelletier E, Camadro JM, Bowler C, Lesuisse E. Endocytosis-mediated siderophore uptake as a strategy for fe acquisition in diatoms. Science Advances. 2018;4:eaar4536. doi: 10.1126/sciadv.aar4536. PubMed DOI PMC

Kazamia E, Mach J, McQuaid J, Olsinova M, Machan R, Coale T, Lesuisse E, Allen A, Sutak R, Bowler C. Monitoring the localization of three iron starvation induced proteins (ISIPs) in a single transformant of Phaeodactylum tricornutum under a range of iron supplementation regimes. The Molecular Life of Diatoms Programme and Abstract Book; 2019. pp. 95–96.

Keeling PJ, Burki F, Wilcox HM, Allam B, Allen EE, Amaral-Zettler LA, Armbrust EV, Archibald JM, Bharti AK, Bell CJ, Beszteri B, Bidle KD, Cameron CT, Campbell L, Caron DA, Cattolico RA, Collier JL, Coyne K, Davy SK, Deschamps P, Dyhrman ST, Edvardsen B, Gates RD, Gobler CJ, Greenwood SJ, Guida SM, Jacobi JL, Jakobsen KS, James ER, Jenkins B, John U, Johnson MD, Juhl AR, Kamp A, Katz LA, Kiene R, Kudryavtsev A, Leander BS, Lin S, Lovejoy C, Lynn D, Marchetti A, McManus G, Nedelcu AM, Menden-Deuer S, Miceli C, Mock T, Montresor M, Moran MA, Murray S, Nadathur G, Nagai S, Ngam PB, Palenik B, Pawlowski J, Petroni G, Piganeau G, Posewitz MC, Rengefors K, Romano G, Rumpho ME, Rynearson T, Schilling KB, Schroeder DC, Simpson AG, Slamovits CH, Smith DR, Smith GJ, Smith SR, Sosik HM, Stief P, Theriot E, Twary SN, Umale PE, Vaulot D, Wawrik B, Wheeler GL, Wilson WH, Xu Y, Zingone A, Worden AZ. The marine microbial eukaryote transcriptome sequencing project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing. PLOS Biology. 2014;12:e1001889. doi: 10.1371/journal.pbio.1001889. PubMed DOI PMC

Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nature Protocols. 2015;10:845–858. doi: 10.1038/nprot.2015.053. PubMed DOI PMC

Kilian O, Kroth PG. Identification and characterization of a new conserved motif within the presequence of proteins targeted into complex diatom plastids. The Plant Journal. 2005;41:175–183. doi: 10.1111/j.1365-313X.2004.02294.x. PubMed DOI

Kim T-W, Park CH, Hsu C-C, Zhu J-Y, Hsiao Y, Branon T, S-l X, Ting AY, Wang Z-Y. Application of TurboID-mediated proximity labeling for mapping a GSK3 kinase signaling network in Arabidopsis. bioRxiv. 2019 doi: 10.1101/636324. DOI

Knoll AH, Bergmann KD, Strauss JV. Life: the first two billion years. Philosophical Transactions of the Royal Society B: Biological Sciences. 2016;371:20150493. doi: 10.1098/rstb.2015.0493. PubMed DOI PMC

Kominek J, Doering DT, Opulente DA, Shen XX, Zhou X, DeVirgilio J, Hulfachor AB, Groenewald M, Mcgee MA, Karlen SD, Kurtzman CP, Rokas A, Hittinger CT. Eukaryotic acquisition of a bacterial operon. Cell. 2019;176:1356–1366. doi: 10.1016/j.cell.2019.01.034. PubMed DOI PMC

Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane protein topology with a hidden markov model: application to complete genomes. Journal of Molecular Biology. 2001;305:567–580. doi: 10.1006/jmbi.2000.4315. PubMed DOI

Kustka AB, Allen AE, Morel FMM. Sequence analysis and transcriptional regulation of Iron acquisition genes in two marine diatoms. Journal of Phycology. 2007;43:715–729. doi: 10.1111/j.1529-8817.2007.00359.x. DOI

Lam SS, Martell JD, Kamer KJ, Deerinck TJ, Ellisman MH, Mootha VK, Ting AY. Directed evolution of APEX2 for electron microscopy and proximity labeling. Nature Methods. 2015;12:51–54. doi: 10.1038/nmeth.3179. PubMed DOI PMC

Lampe RH, Mann EL, Cohen NR, Till CP, Thamatrakoln K, Brzezinski MA, Bruland KW, Twining BS, Marchetti A. Different iron storage strategies among bloom-forming diatoms. PNAS. 2018;115:E12275–E12284. doi: 10.1073/pnas.1805243115. PubMed DOI PMC

Leynaert A, Bucciarelli E, Claquin P, Dugdale RC, Martin-Jézéquel V, Pondaven P, Ragueneau O. Effect of iron deficiency on diatom cell size and silicic acid uptake kinetics. Limnology and Oceanography. 2004;49:1134–1143. doi: 10.4319/lo.2004.49.4.1134. DOI

Li Y, Tian C, Liu K, Zhou Y, Yang J, Zou P. A clickable APEX probe for Proximity-Dependent proteomic profiling in yeast. Cell Chemical Biology. 2020;27:858–865. doi: 10.1016/j.chembiol.2020.05.006. PubMed DOI

Lindquist E, Aronsson H. Chloroplast vesicle transport. Photosynthesis Research. 2018;138:361–371. doi: 10.1007/s11120-018-0566-0. PubMed DOI PMC

Lommer M, Specht M, Roy AS, Kraemer L, Andreson R, Gutowska MA, Wolf J, Bergner SV, Schilhabel MB, Klostermeier UC, Beiko RG, Rosenstiel P, Hippler M, LaRoche J. Genome and low-iron response of an oceanic diatom adapted to chronic iron limitation. Genome Biology. 2012;13:R66. doi: 10.1186/gb-2012-13-7-r66. PubMed DOI PMC

López-Millán AF, Duy D, Philippar K. Chloroplast iron transport proteins - Function and impact on plant physiology. Frontiers in Plant Science. 2016;7:178. doi: 10.3389/fpls.2016.00178. PubMed DOI PMC

Lundberg E, Borner GHH. Spatial proteomics: a powerful discovery tool for cell biology. Nature Reviews Molecular Cell Biology. 2019;20:285–302. doi: 10.1038/s41580-018-0094-y. PubMed DOI

Mair A, Xu SL, Branon TC, Ting AY, Bergmann DC. Proximity labeling of protein complexes and cell-type-specific organellar proteomes in Arabidopsis enabled by TurboID. eLife. 2019;8:e47864. doi: 10.7554/eLife.47864. PubMed DOI PMC

Marchand J, Heydarizadeh P, Schoefs B, Spetea C. Ion and metabolite transport in the chloroplast of algae: lessons from land plants. Cellular and Molecular Life Sciences. 2018;75:2153–2176. doi: 10.1007/s00018-018-2793-0. PubMed DOI PMC

Marchetti A, Schruth DM, Durkin CA, Parker MS, Kodner RB, Berthiaume CT, Morales R, Allen AE, Armbrust EV. Comparative metatranscriptomics identifies molecular bases for the physiological responses of phytoplankton to varying iron availability. PNAS. 2012;109:E317–E325. doi: 10.1073/pnas.1118408109. PubMed DOI PMC

Martell JD, Deerinck TJ, Sancak Y, Poulos TL, Mootha VK, Sosinsky GE, Ellisman MH, Ting AY. Engineered ascorbate peroxidase as a genetically encoded reporter for electron microscopy. Nature Biotechnology. 2012;30:1143–1148. doi: 10.1038/nbt.2375. PubMed DOI PMC

Martell JD, Deerinck TJ, Lam SS, Ellisman MH, Ting AY. Electron microscopy using the genetically encoded APEX2 tag in cultured mammalian cells. Nature Protocols. 2017;12:1792–1816. doi: 10.1038/nprot.2017.065. PubMed DOI PMC

Martin JH, Coale KH, Johnson KS, Fitzwater SE, Gordon RM, Tanner SJ, Hunter CN, Elrod VA, Nowicki JL, Coley TL, Barber RT, Lindley S, Watson AJ, Van Scoy K, Law CS, Liddicoat MI, Ling R, Stanton T, Stockel J, Collins C, Anderson A, Bidigare R, Ondrusek M, Latasa M, Millero FJ, Lee K, Yao W, Zhang JZ, Friederich G, Sakamoto C, Chavez F, Buck K, Kolber Z, Greene R, Falkowski P, Chisholm SW, Hoge F, Swift R, Yungel J, Turner S, Nightingale P, Hatton A, Liss P, Tindale NW. Testing the iron hypothesis in ecosystems of the equatorial pacific ocean. Nature. 1994;371:123–129. doi: 10.1038/371123a0. DOI

Matsuda Y, Hopkinson BM, Nakajima K, Dupont CL, Tsuji Y. Mechanisms of carbon dioxide acquisition and CO2sensing in marine diatoms: a gateway to carbon metabolism. Philosophical Transactions of the Royal Society B: Biological Sciences. 2017;372:20160403. doi: 10.1098/rstb.2016.0403. PubMed DOI PMC

Maxson ME, Grinstein S. The vacuolar-type H⁺-ATPase at a glance - more than a proton pump. Journal of Cell Science. 2014;127:4987–4993. doi: 10.1242/jcs.158550. PubMed DOI

May T, Soll J. Positive charges determine the topology and functionality of the transmembrane domain in the chloroplastic outer envelope protein Toc34. Journal of Cell Biology. 1998;141:895–904. doi: 10.1083/jcb.141.4.895. PubMed DOI PMC

Mayle KM, Le AM, Kamei DT. The intracellular trafficking pathway of transferrin. Biochimica Et Biophysica Acta (BBA) - General Subjects. 2012;1820:264–281. doi: 10.1016/j.bbagen.2011.09.009. PubMed DOI PMC

McAlister GC, Nusinow DP, Jedrychowski MP, Wühr M, Huttlin EL, Erickson BK, Rad R, Haas W, Gygi SP. MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of differential expression across Cancer cell line proteomes. Analytical Chemistry. 2014;86:7150–7158. doi: 10.1021/ac502040v. PubMed DOI PMC

McQuaid JB, Kustka AB, Oborník M, Horák A, McCrow JP, Karas BJ, Zheng H, Kindeberg T, Andersson AJ, Barbeau KA, Allen AE. Carbonate-sensitive phytotransferrin controls high-affinity iron uptake in diatoms. Nature. 2018;555:534–537. doi: 10.1038/nature25982. PubMed DOI

Merchant S. Nutritional copper signaling and homeostasis. [April 24, 2020];Grantome Research Proposal Abstract. 2019 http://grantome.com/grant/NIH/R35-GM127114-01

Merkulova M, Hurtado-Lorenzo A, Hosokawa H, Zhuang Z, Brown D, Ausiello DA, Marshansky V. Aldolase directly interacts with ARNO and modulates cell morphology and acidic vesicle distribution. American Journal of Physiology-Cell Physiology. 2011;300:C1442–C1455. doi: 10.1152/ajpcell.00076.2010. PubMed DOI PMC

Mészáros B, Erdos G, Dosztányi Z. IUPred2A: context-dependent prediction of protein disorder as a function of redox state and protein binding. Nucleic Acids Research. 2018;46:W329–W337. doi: 10.1093/nar/gky384. PubMed DOI PMC

Morel FMM, Kustka AB, Shaked Y. The role of unchelated fe in the iron nutrition of phytoplankton. Limnology and Oceanography. 2008;53:400–404. doi: 10.4319/lo.2008.53.1.0400. DOI

Moreno CM, Lin Y, Davies S, Monbureau E, Cassar N, Marchetti A. Examination of gene repertoires and physiological responses to iron and light limitation in southern ocean diatoms. Polar Biology. 2018;41:679–696. doi: 10.1007/s00300-017-2228-7. DOI

Morrissey J, Sutak R, Paz-Yepes J, Tanaka A, Moustafa A, Veluchamy A, Thomas Y, Botebol H, Bouget FY, McQuaid JB, Tirichine L, Allen AE, Lesuisse E, Bowler C. A novel protein, ubiquitous in marine phytoplankton, concentrates iron at the cell surface and facilitates uptake. Current Biology. 2015;25:364–371. doi: 10.1016/j.cub.2014.12.004. PubMed DOI

Musayev FN, Di Salvo ML, Ko TP, Schirch V, Safo MK. Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. Protein Science. 2003;12:1455–1463. doi: 10.1110/ps.0356203. PubMed DOI PMC

Naslavsky N, Caplan S. The enigmatic endosome - sorting the ins and outs of endocytic trafficking. Journal of Cell Science. 2018;131:jcs216499. doi: 10.1242/jcs.216499. PubMed DOI PMC

Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Molecular Biology and Evolution. 2015;32:268–274. doi: 10.1093/molbev/msu300. PubMed DOI PMC

Nützmann HW, Scazzocchio C, Osbourn A. Metabolic gene clusters in eukaryotes. Annual Review of Genetics. 2018;52:159–183. doi: 10.1146/annurev-genet-120417-031237. PubMed DOI

O'Halloran TV, Culotta VC. Metallochaperones, an intracellular shuttle service for metal ions. Journal of Biological Chemistry. 2000;275:25057–25060. doi: 10.1074/jbc.R000006200. PubMed DOI

O'Leary NA, Wright MW, Brister JR, Ciufo S, Haddad D, McVeigh R, Rajput B, Robbertse B, Smith-White B, Ako-Adjei D, Astashyn A, Badretdin A, Bao Y, Blinkova O, Brover V, Chetvernin V, Choi J, Cox E, Ermolaeva O, Farrell CM, Goldfarb T, Gupta T, Haft D, Hatcher E, Hlavina W, Joardar VS, Kodali VK, Li W, Maglott D, Masterson P, McGarvey KM, Murphy MR, O'Neill K, Pujar S, Rangwala SH, Rausch D, Riddick LD, Schoch C, Shkeda A, Storz SS, Sun H, Thibaud-Nissen F, Tolstoy I, Tully RE, Vatsan AR, Wallin C, Webb D, Wu W, Landrum MJ, Kimchi A, Tatusova T, DiCuccio M, Kitts P, Murphy TD, Pruitt KD. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Research. 2016;44:D733–D745. doi: 10.1093/nar/gkv1189. PubMed DOI PMC

Och LM, Shields-Zhou GA. The neoproterozoic oxygenation event: environmental perturbations and biogeochemical cycling. Earth-Science Reviews. 2012;110:26–57. doi: 10.1016/j.earscirev.2011.09.004. DOI

Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, Chen J, Sharp JJ, Fujiwara Y, Barker JE, Fleming MD. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nature Genetics. 2005;37:1264–1269. doi: 10.1038/ng1658. PubMed DOI PMC

Osbourn AE, Field B. Operons. Cellular and Molecular Life Sciences. 2009;66:3755–3775. doi: 10.1007/s00018-009-0114-3. PubMed DOI PMC

Otsuka Y, Satoh T, Nakayama N, Inaba R, Yamashita H, Satoh AK. Parcas is the predominant Rab11-GEF for rhodopsin transport in Drosophila photoreceptors. Journal of Cell Science. 2019;132:jcs231431. doi: 10.1242/jcs.231431. PubMed DOI

Paek J, Kalocsay M, Staus DP, Wingler L, Pascolutti R, Paulo JA, Gygi SP, Kruse AC. Multidimensional tracking of GPCR signaling via Peroxidase-Catalyzed proximity labeling. Cell. 2017;169:338–349. doi: 10.1016/j.cell.2017.03.028. PubMed DOI PMC

Paulo JA, O'Connell JD, Everley RA, O'Brien J, Gygi MA, Gygi SP. Quantitative mass spectrometry-based multiplexing compares the abundance of 5000 S. cerevisiae proteins across 10 carbon sources. Journal of Proteomics. 2016;148:85–93. doi: 10.1016/j.jprot.2016.07.005. PubMed DOI PMC

Peng K, Radivojac P, Vucetic S, Dunker AK, Obradovic Z. Length-dependent prediction of protein intrinsic disorder. BMC Bioinformatics. 2006;7:208. doi: 10.1186/1471-2105-7-208. PubMed DOI PMC

Perez-Riverol Y, Csordas A, Bai J, Bernal-Llinares M, Hewapathirana S, Kundu DJ, Inuganti A, Griss J, Mayer G, Eisenacher M, Pérez E, Uszkoreit J, Pfeuffer J, Sachsenberg T, Yilmaz S, Tiwary S, Cox J, Audain E, Walzer M, Jarnuczak AF, Ternent T, Brazma A, Vizcaíno JA. The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Research. 2019;47:D442–D450. doi: 10.1093/nar/gky1106. PubMed DOI PMC

Peschke M, Moog D, Klingl A, Maier UG, Hempel F. Evidence for glycoprotein transport into complex plastids. PNAS. 2013;110:10860–10865. doi: 10.1073/pnas.1301945110. PubMed DOI PMC

Petersen TN, Brunak S, von Heijne G, Nielsen H. SignalP 4.0: discriminating signal peptides from transmembrane regions. Nature Methods. 2011;8:785–786. doi: 10.1038/nmeth.1701. PubMed DOI

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF chimera--a visualization system for exploratory research and analysis. Journal of Computational Chemistry. 2004;25:1605–1612. doi: 10.1002/jcc.20084. PubMed DOI

Philpott CC, Jadhav S. The ins and outs of iron: escorting iron through the mammalian cytosol. Free Radical Biology and Medicine. 2019;133:112–117. doi: 10.1016/j.freeradbiomed.2018.10.411. PubMed DOI

Poole LB. The basics of thiols and cysteines in redox biology and chemistry. Free Radical Biology and Medicine. 2015;80:148–157. doi: 10.1016/j.freeradbiomed.2014.11.013. PubMed DOI PMC

Prihoda J, Tanaka A, de Paula WB, Allen JF, Tirichine L, Bowler C. Chloroplast-mitochondria cross-talk in diatoms. Journal of Experimental Botany. 2012;63:1543–1557. doi: 10.1093/jxb/err441. PubMed DOI

Progida C, Bakke O. Bidirectional traffic between the golgi and the endosomes - machineries and regulation. Journal of Cell Science. 2016;129:jcs.185702–3982. doi: 10.1242/jcs.185702. PubMed DOI

Przybyla-Toscano J, Roland M, Gaymard F, Couturier J, Rouhier N. Roles and maturation of iron-sulfur proteins in plastids. JBIC Journal of Biological Inorganic Chemistry. 2018;23:545–566. doi: 10.1007/s00775-018-1532-1. PubMed DOI PMC

R Development Core Team . Vienna, Austria: R Foundation for Statistical Computing; 2013. http://www.R-project.org/

Radhamony RN, Theg SM. Evidence for an ER to Golgi to chloroplast protein transport pathway. Trends in Cell Biology. 2006;16:385–387. doi: 10.1016/j.tcb.2006.06.003. PubMed DOI

Rao RS, Bernd W. Do N-glycoproteins have preference for specific sequons? Bioinformation. 2010;5:208–212. doi: 10.6026/97320630005208. PubMed DOI PMC

Raven EL. Understanding functional diversity and substrate specificity in haem peroxidases: what can we learn from ascorbate peroxidase? Natural Product Reports. 2003;20:367–381. doi: 10.1039/b210426c. PubMed DOI

Ree R, Varland S, Arnesen T. Spotlight on protein N-terminal acetylation. Experimental & Molecular Medicine. 2018;50:1–13. doi: 10.1038/s12276-018-0116-z. PubMed DOI PMC

Rhee HW, Zou P, Udeshi ND, Martell JD, Mootha VK, Carr SA, Ting AY. Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science. 2013;339:1328–1331. doi: 10.1126/science.1230593. PubMed DOI PMC

Rochaix JD. Regulation of photosynthetic electron transport. Biochimica Et Biophysica Acta (BBA) - Bioenergetics. 2011;1807:375–383. doi: 10.1016/j.bbabio.2010.11.010. PubMed DOI

Rosenzweig AC. Metallochaperones: bind and deliver. Chemistry & Biology. 2002;9:673–677. doi: 10.1016/s1074-5521(02)00156-4. PubMed DOI

Sacher M, Di Bacco A, Lunin VV, Ye Z, Wagner J, Gill G, Cygler M. The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation. PNAS. 2005;102:18326–18331. doi: 10.1073/pnas.0505071102. PubMed DOI PMC

Sapriel G, Quinet M, Heijde M, Jourdren L, Tanty V, Luo G, Le Crom S, Lopez PJ. Genome-wide transcriptome analyses of silicon metabolism in Phaeodactylum tricornutum reveal the multilevel regulation of silicic acid transporters. PLOS ONE. 2009;4:e7458. doi: 10.1371/journal.pone.0007458. PubMed DOI PMC

Savelli B, Li Q, Webber M, Jemmat AM, Robitaille A, Zamocky M, Mathé C, Dunand C. RedoxiBase: a database for ROS homeostasis regulated proteins. Redox Biology. 2019;26:101247. doi: 10.1016/j.redox.2019.101247. PubMed DOI PMC

Savitsky P, Bray J, Cooper CD, Marsden BD, Mahajan P, Burgess-Brown NA, Gileadi O. High-throughput production of human proteins for crystallization: the SGC experience. Journal of Structural Biology. 2010;172:3–13. doi: 10.1016/j.jsb.2010.06.008. PubMed DOI PMC

Schähs P, Weidinger P, Probst OC, Svoboda B, Stadlmann J, Beug H, Waerner T, Mach L. Cellular repressor of E1A-stimulated genes is a bona fide lysosomal protein which undergoes proteolytic maturation during its biosynthesis. Experimental Cell Research. 2008;314:3036–3047. doi: 10.1016/j.yexcr.2008.06.015. PubMed DOI

Scheiber IF, Pilátová J, Malych R, Kotabova E, Krijt M, Vyoral D, Mach J, Léger T, Camadro JM, Prášil O, Lesuisse E, Sutak R. Copper and iron metabolism in Ostreococcus tauri - the role of Phytotransferrin, plastocyanin and a chloroplast copper-transporting ATPase. Metallomics. 2019;11:1657–1666. doi: 10.1039/C9MT00078J. PubMed DOI

Sengupta R, Poderycki MJ, Mattoo S. CryoAPEX - an electron tomography tool for subcellular localization of membrane proteins. Journal of Cell Science. 2019;132:jcs222315. doi: 10.1242/jcs.222315. PubMed DOI PMC

Sheppard VC, Scheffel A, Poulsen N, Kröger N. Live diatom silica immobilization of multimeric and redox-active enzymes. Applied and Environmental Microbiology. 2012;78:211–218. doi: 10.1128/AEM.06698-11. PubMed DOI PMC

Shoemaker BA, Portman JJ, Wolynes PG. Speeding molecular recognition by using the folding funnel: the fly-casting mechanism. PNAS. 2000;97:8868–8873. doi: 10.1073/pnas.160259697. PubMed DOI PMC

Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins DG. Fast, scalable generation of high-quality protein multiple sequence alignments using clustal omega. Molecular Systems Biology. 2011;7:539. doi: 10.1038/msb.2011.75. PubMed DOI PMC

Smith SR, Gillard JT, Kustka AB, McCrow JP, Badger JH, Zheng H, New AM, Dupont CL, Obata T, Fernie AR, Allen AE. Transcriptional orchestration of the global cellular response of a model pennate diatom to diel light cycling under iron limitation. PLOS Genetics. 2016;12:e1006490. doi: 10.1371/journal.pgen.1006490. PubMed DOI PMC

Soll J, Schleiff E. Protein import into chloroplasts. Nature Reviews Molecular Cell Biology. 2004;5:198–208. doi: 10.1038/nrm1333. PubMed DOI

Steentoft C, Vakhrushev SY, Joshi HJ, Kong Y, Vester-Christensen MB, Schjoldager KT, Lavrsen K, Dabelsteen S, Pedersen NB, Marcos-Silva L, Gupta R, Bennett EP, Mandel U, Brunak S, Wandall HH, Levery SB, Clausen H. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology. The EMBO Journal. 2013;32:1478–1488. doi: 10.1038/emboj.2013.79. PubMed DOI PMC

Strand TA, Lale R, Degnes KF, Lando M, Valla S. A new and improved host-independent plasmid system for RK2-based conjugal transfer. PLOS ONE. 2014;9:e90372. doi: 10.1371/journal.pone.0090372. PubMed DOI PMC

Tagliabue A, Bowie AR, Boyd PW, Buck KN, Johnson KS, Saito MA. The integral role of iron in ocean biogeochemistry. Nature. 2017;543:51–59. doi: 10.1038/nature21058. PubMed DOI

Tara Oceans Coordinators. Carradec Q, Pelletier E, Da Silva C, Alberti A, Seeleuthner Y, Blanc-Mathieu R, Lima-Mendez G, Rocha F, Tirichine L, Labadie K, Kirilovsky A, Bertrand A, Engelen S, Madoui MA, Méheust R, Poulain J, Romac S, Richter DJ, Yoshikawa G, Dimier C, Kandels-Lewis S, Picheral M, Searson S, Jaillon O, Aury JM, Karsenti E, Sullivan MB, Sunagawa S, Bork P, Not F, Hingamp P, Raes J, Guidi L, Ogata H, de Vargas C, Iudicone D, Bowler C, Wincker P. A global ocean atlas of eukaryotic genes. Nature Communications. 2018;9:373. doi: 10.1038/s41467-017-02342-1. PubMed DOI PMC

Tesson B, Genet MJ, Fernandez V, Degand S, Rouxhet PG, Martin-Jézéquel V. Surface chemical composition of diatoms. ChemBioChem. 2009;10:2011–2024. doi: 10.1002/cbic.200800811. PubMed DOI

Theorell H. Preparation in pure state of the effect group of yellow enzymes. Biochemische Zeitschrift. 1935;275:344–346.

Trinkle-Mulcahy L. Recent advances in proximity-based labeling methods for interactome mapping. F1000Research. 2019;8:F1000. doi: 10.12688/f1000research.16903.1. PubMed DOI PMC

Tuteja R. Type I signal peptidase: an overview. Archives of Biochemistry and Biophysics. 2005;441:107–111. doi: 10.1016/j.abb.2005.07.013. PubMed DOI

Uversky VN. The intrinsic disorder alphabet. III. dual personality of serine. Intrinsically Disordered Proteins. 2015a;3:e1027032. doi: 10.1080/21690707.2015.1027032. PubMed DOI PMC

Uversky VN. The multifaceted roles of intrinsic disorder in protein complexes. FEBS Letters. 2015b;589:2498–2506. doi: 10.1016/j.febslet.2015.06.004. PubMed DOI

Uversky VN. Dancing protein clouds: the strange biology and chaotic physics of intrinsically disordered proteins. Journal of Biological Chemistry. 2016;291:6681–6688. doi: 10.1074/jbc.R115.685859. PubMed DOI PMC

Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Current Medicinal Chemistry. 2005;12:1161–1208. doi: 10.2174/0929867053764635. PubMed DOI

Villarejo A, Burén S, Larsson S, Déjardin A, Monné M, Rudhe C, Karlsson J, Jansson S, Lerouge P, Rolland N, von Heijne G, Grebe M, Bako L, Samuelsson G. Evidence for a protein transported through the secretory pathway en route to the higher plant chloroplast. Nature Cell Biology. 2005;7:1224–1231. doi: 10.1038/ncb1330. PubMed DOI

Wang L, Jonikas MC. The pyrenoid. Current Biology. 2020;30:R456–R458. doi: 10.1016/j.cub.2020.02.051. PubMed DOI

Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochemical Journal. 2011;434:365–381. doi: 10.1042/BJ20101825. PubMed DOI PMC

Yee DP, Hildebrand M, Tresguerres M. Dynamic subcellular translocation of V-type H+ -ATPase is essential for biomineralization of the diatom silica cell wall. New Phytologist. 2020;225:2411–2422. doi: 10.1111/nph.16329. PubMed DOI

Zak O, Ikuta K, Aisen P. The synergistic anion-binding sites of human transferrin: chemical and physiological effects of site-directed mutagenesis. Biochemistry. 2002;41:7416–7423. doi: 10.1021/bi0160258. PubMed DOI

Zhang Y, Song G, Lal NK, Nagalakshmi U, Li Y, Zheng W, Huang PJ, Branon TC, Ting AY, Walley JW, Dinesh-Kumar SP. TurboID-based proximity labeling reveals that UBR7 is a regulator of N NLR immune receptor-mediated immunity. Nature Communications. 2019;10:3252. doi: 10.1038/s41467-019-11202-z. PubMed DOI PMC

Zulu NN, Zienkiewicz K, Vollheyde K, Feussner I. Current trends to comprehend lipid metabolism in diatoms. Progress in Lipid Research. 2018;70:1–16. doi: 10.1016/j.plipres.2018.03.001. PubMed DOI

Short-term acidification promotes diverse iron acquisition and conservation mechanisms in upwelling-associated phytoplankton

In vivo localization of iron starvation induced proteins under variable iron supplementation regimes in Phaeodactylum tricornutum

Complex Response of the Chlorarachniophyte Bigelowiella natans to Iron Availability