BACKGROUND: The presence of mitochondria is a distinguishing feature between prokaryotic and eukaryotic cells. It is currently accepted that the evolutionary origin of mitochondria coincided with the formation of eukaryotes and from that point control of mitochondrial inheritance was required. Yet, the way the mitochondrial presence has been maintained throughout the eukaryotic cell cycle remains a matter of study. Eukaryotes control mitochondrial inheritance mainly due to the presence of the genetic component; still only little is known about the segregation of mitochondria to daughter cells during cell division. Additionally, anaerobic eukaryotic microbes evolved a variety of genomeless mitochondria-related organelles (MROs), which could be theoretically assembled de novo, providing a distinct mechanistic basis for maintenance of stable mitochondrial numbers. Here, we approach this problem by studying the structure and inheritance of the protist Giardia intestinalis MROs known as mitosomes. RESULTS: We combined 2D stimulated emission depletion (STED) microscopy and focused ion beam scanning electron microscopy (FIB/SEM) to show that mitosomes exhibit internal segmentation and conserved asymmetric structure. From a total of about forty mitosomes, a small, privileged population is harnessed to the flagellar apparatus, and their life cycle is coordinated with the maturation cycle of G. intestinalis flagella. The orchestration of mitosomal inheritance with the flagellar maturation cycle is mediated by a microtubular connecting fiber, which physically links the privileged mitosomes to both axonemes of the oldest flagella pair and guarantees faithful segregation of the mitosomes into the daughter cells. CONCLUSION: Inheritance of privileged Giardia mitosomes is coupled to the flagellar maturation cycle. We propose that the flagellar system controls segregation of mitochondrial organelles also in other members of this supergroup (Metamonada) of eukaryotes and perhaps reflects the original strategy of early eukaryotic cells to maintain this key organelle before mitochondrial fusion-fission dynamics cycle as observed in Metazoa was established.

Department of Biology 1 Biocenter of Ludwig Maximilians University Munich Germany

Department of Parasitology Faculty of Science Charles University BIOCEV Vestec Czech Republic

Institute of Immunology and Microbiology 1st Faculty of Medicine Charles University Prague Czech Republic

Plant Development and Electron Microscopy Department of Biology 1 Biocenter of Ludwig Maximilians University Munich Germany

Zobrazit více v PubMed

Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nature Cell Biology. 2018;20(7):745–754. doi: 10.1038/s41556-018-0124-1. PubMed DOI PMC

Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science. 2012;337(6098):1062–1065. doi: 10.1126/science.1219855. PubMed DOI PMC

Friedman JR, Nunnari J. Mitochondrial form and function. Nature. 2014;505(7483):335–343. doi: 10.1038/nature12985. PubMed DOI PMC

Labbé K, Murley A, Nunnari J. Determinants and functions of mitochondrial behavior. Annu Rev Cell Dev Biol. 2014;30(1):357–391. doi: 10.1146/annurev-cellbio-101011-155756. PubMed DOI

Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12(1):9–14. doi: 10.1038/nrm3028. PubMed DOI PMC

Mishra P, Chan DC. Mitochondrial dynamics and inheritance during cell division, development and disease. Nat Rev Mol Cell Biol. 2014;15(10):634–646. doi: 10.1038/nrm3877. PubMed DOI PMC

Voleman L, Doležal P. Mitochondrial dynamics in parasitic protists. PLoS Pathog. 2019;15(11):e1008008. doi: 10.1371/journal.ppat.1008008. PubMed DOI PMC

Arimura SI. Fission and fusion of plant mitochondria, and genome maintenance. Plant Physiology. 2018;176(1):152–161. doi: 10.1104/pp.17.01025. PubMed DOI PMC

Uchiumi Y, Ohtsuki H, Sasaki A. Evolution of self-limited cell division of symbionts. Proc R Soc B Biol Sci. 2019;286(1895):20182238. doi: 10.1098/rspb.2018.2238. PubMed DOI PMC

Atkinson AW, John PCL, Gunning BES. The growth and division of the single mitochondrion and other organelles during the cell cycle of Chlorella, studied by quantitative stereology and three dimensional reconstruction. Protoplasma. 1974;81(1):77–109. doi: 10.1007/BF02055775. PubMed DOI

Vickerman K. DNA throughout the single mitochondrion of a kinetoplastid flagellate: observations on the ultrastructure of Cryptobia vaginalis (Hesse, 1910) J Protozool. 1977;24(2):221–233. doi: 10.1111/j.1550-7408.1977.tb00970.x. DOI

Seeber F, Limenitakis J, Soldati-Favre D. Apicomplexan mitochondrial metabolism: a story of gains, losses and retentions. Trends in Parasitology. 2008;24(10):468–478. doi: 10.1016/j.pt.2008.07.004. PubMed DOI

Letcher PM, Powell MJ. Kappamyces, a new genus in the Chytridiales (Chytridiomycota) Nov Hedwigia. 2005;80(1-2):115–133. doi: 10.1127/0029-5035/2005/0080-0115. DOI

Robinson DR, Gull K. Basal body movements as a mechanism for mitochondrial genome segregation in the trypanosome cell cycle. Nature. 1991;352(6337):731–733. doi: 10.1038/352731a0. PubMed DOI

Schneider A, Ochsenreiter T. Failure is not an option – mitochondrial genome segregation in trypanosomes. J Cell Sci. 2018;131:jcs221820. doi:10.1242/jcs.221820. PubMed

Zhao Z, Lindsay ME, Roy Chowdhury A, Robinson DR, Englund PT. p166, a link between the trypanosome mitochondrial DNA and flagellum, mediates genome segregation. EMBO J. 2008;27(1):143–154. doi: 10.1038/sj.emboj.7601956. PubMed DOI PMC

Ogbadoyi EO, Robinson DR, Gull K. A high-order trans-membrane structural linkage is responsible for mitochondrial genome positioning and segregation by flagellar basal bodies in trypanosomes. Mol Biol Cell. 2003;14(5):1769–1779. doi: 10.1091/mbc.e02-08-0525. PubMed DOI PMC

Jakob M, Hoffmann A, Amodeo S, Peitsch C, Zuber B, Ochsenreiter T. Mitochondrial growth during the cell cycle of Trypanosoma brucei bloodstream forms. Sci Rep. 2016;6(1):36565. doi: 10.1038/srep36565. PubMed DOI PMC

Hoffmann A, Käser S, Jakob M, Amodeo S, Peitsch C, Týc Í, et al. Molecular model of the mitochondrial genome segregation machinery in Trypanosoma brucei. Proc Natl Acad Sci. 2018;115(8):1–10. doi: 10.1073/pnas.1716582115. PubMed DOI PMC

Schnarwiler F, Niemann M, Doiron N, Harsman A, Kaser S, Mani J, Chanfon A, Dewar CE, Oeljeklaus S, Jackson CB, Pusnik M, Schmidt O, Meisinger C, Hiller S, Warscheid B, Schnaufer AC, Ochsenreiter T, Schneider A. Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance. Proc Natl Acad Sci. 2014;111(21):7624–7629. doi: 10.1073/pnas.1404854111. PubMed DOI PMC

Käser S, Willemin M, Schnarwiler F, Schimanski B, Poveda-Huertes D, Oeljeklaus S, Haenni B, Zuber B, Warscheid B, Meisinger C, Schneider A. Biogenesis of the mitochondrial DNA inheritance machinery in the mitochondrial outer membrane of Trypanosoma brucei. PLoS Pathog. 2017;13(12):e1006808. doi: 10.1371/journal.ppat.1006808. PubMed DOI PMC

Trikin R, Doiron N, Hoffmann A, Haenni B, Jakob M, Schnaufer A, Schimanski B, Zuber B, Ochsenreiter T. TAC102 is a novel component of the mitochondrial genome segregation machinery in trypanosomes. PLoS Pathog. 2016;12(5):1005586. doi: 10.1371/journal.ppat.1005586. PubMed DOI PMC

Adl SM, Bass D, Lane CE, Lukeš J, Schoch CL, Smirnov A, Agatha S, Berney C, Brown MW, Burki F, Cárdenas P, Čepička I, Chistyakova L, Campo J, Dunthorn M, Edvardsen B, Eglit Y, Guillou L, Hampl V, Heiss AA, Hoppenrath M, James TY, Karnkowska A, Karpov S, Kim E, Kolisko M, Kudryavtsev A, Lahr DJG, Lara E, le Gall L, Lynn DH, Mann DG, Massana R, Mitchell EAD, Morrow C, Park JS, Pawlowski JW, Powell MJ, Richter DJ, Rueckert S, Shadwick L, Shimano S, Spiegel FW, Torruella G, Youssef N, Zlatogursky V, Zhang Q. Revisions to the classification, nomenclature, and diversity of eukaryotes. J Eukaryot Microbiol. 2019;66(1):4–119. doi: 10.1111/jeu.12691. PubMed DOI PMC

Roger AJ, Muñoz-Gómez SA, Kamikawa R. The origin and diversification of mitochondria. Curr Biol. 2017;27(21):R1177–R1192. doi: 10.1016/j.cub.2017.09.015. PubMed DOI

Tovar J, León-Avila G, Sánchez LB, Sutak R, Tachezy J, van der Giezen M, Hernández M, Müller M, Lucocq JM. Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation. Nature. 2003;426(6963):172–176. doi: 10.1038/nature01945. PubMed DOI

Rout S, Zumthor JP, Schraner EM, Faso C, Hehl AB. An interactome-centered protein discovery approach reveals novel components involved in mitosome function and homeostasis in Giardia lamblia. PLOS Pathog. 2016;12(12):e1006036. doi: 10.1371/journal.ppat.1006036. PubMed DOI PMC

Martincová E, Voleman L, Najdrová V, De Napoli M, Eshar S, Gualdron M, et al. Live imaging of mitosomes and hydrogenosomes by HaloTag technology. PLoS One. 2012;7(4):e36314. doi: 10.1371/journal.pone.0036314. PubMed DOI PMC

Voleman L, Najdrová V, Ástvaldsson Á, Tůmová P, Einarsson E, Švindrych Z, Hagen GM, Tachezy J, Svärd SG, Doležal P. Giardia intestinalis mitosomes undergo synchronized fission but not fusion and are constitutively associated with the endoplasmic reticulum. BMC Biol. 2017;15(1):27. doi: 10.1186/s12915-017-0361-y. PubMed DOI PMC

Regoes A, Zourmpanou D, León-Avila G, van der Giezen M, Tovar J, Hehl AB. Protein import, replication, and inheritance of a vestigial mitochondrion. J Biol Chem. 2005;280(34):30557–30563. doi: 10.1074/jbc.M500787200. PubMed DOI

Dagley MJ, Dolezal P, Likic VA, Smid O, Purcell AW, Buchanan SK, Tachezy J, Lithgow T. The protein import channel in the outer mitosomal membrane of Giardia intestinalis. Mol Biol Evol. 2009;26(9):1941–1947. doi: 10.1093/molbev/msp117. PubMed DOI PMC

Pyrihová E, Motyčková A, Voleman L, Wandyszewska N, Fišer R, Seydlová G, Roger A, Kolísko M, Doležal P. A single Tim translocase in the mitosomes of Giardia intestinalis illustrates convergence of protein import machines in anaerobic eukaryotes. Genome Biol Evol. 2018;10(10):2813–2822. doi: 10.1093/gbe/evy215. PubMed DOI PMC

Midlej V, Penha L, Silva R, de Souza W, Benchimol M. Mitosomal chaperone modulation during the life cycle of the pathogenic protist Giardia intestinalis. Eur J Cell Biol. 2016;95(12):531–542. doi: 10.1016/j.ejcb.2016.08.005. PubMed DOI

Hehl AB, Regos A, Schraner E, Schneider A. Bax function in the absence of mitochondria in the primitive protozoan Giardia lamblia. PLoS One. 2007;2(5):e488. doi: 10.1371/journal.pone.0000488. PubMed DOI PMC

Plamont M-A, Billon-Denis E, Maurin S, Gauron C, Pimenta FM, Specht CG, Shi J, Quérard J, Pan B, Rossignol J, Moncoq K, Morellet N, Volovitch M, Lescop E, Chen Y, Triller A, Vriz S, le Saux T, Jullien L, Gautier A. Small fluorescence-activating and absorption-shifting tag for tunable protein imaging in vivo. Proc Natl Acad Sci U S A. 2016;113(3):497–502. doi: 10.1073/pnas.1513094113. PubMed DOI PMC

Sagolla MS, Dawson SC, Mancuso JJ, Cande WZ. Three-dimensional analysis of mitosis and cytokinesis in the binucleate parasite Giardia intestinalis. J Cell Sci. 2006;119(Pt 23):4889–4900. doi: 10.1242/jcs.03276. PubMed DOI

Nohynková E, Tumová P, Kulda J. Cell division of Giardia intestinalis: flagellar developmental cycle involves transformation and exchange of flagella between mastigonts of a diplomonad cell. Eukaryot Cell. 2006;5(4):753–761. doi: 10.1128/EC.5.4.753-761.2006. PubMed DOI PMC

Tůmová P, Hofštetrová K, Nohýnková E, Hovorka O, Král J. Cytogenetic evidence for diversity of two nuclei within a single diplomonad cell of Giardia. Chromosoma. 2007;116(1):65–78. doi: 10.1007/s00412-006-0082-4. PubMed DOI

Heine J, Reuss M, Harke B, D’Este E, Sahl SJ, Hell SW. Adaptive-illumination STED nanoscopy. Proc Natl Acad Sci U S A. 2017;114(37):9797–9802. doi: 10.1073/pnas.1708304114. PubMed DOI PMC

Luckner M, Wanner G. Precise and economic FIB/SEM for CLEM: with 2 nm voxels through mitosis. Histochem Cell Biol. 2018;150(2):149–170. doi: 10.1007/s00418-018-1681-x. PubMed DOI PMC

Tůmová P, Nohýnková E, Klingl A, Wanner G. A rapid workflow for the characterization of small numbers of unicellular eukaryotes by using correlative light and electron microscopy. J Microbiol Methods. 2020;172:105888. doi: 10.1016/j.mimet.2020.105888. PubMed DOI

Faso C, Hehl AB. A cytonaut’s guide to protein trafficking in Giardia lamblia. In: Advances in Parasitology. Academic Press; 2019. A cytonaut's guide to protein trafficking in Giardia lamblia; pp. 105–127. PubMed

Touz MC. The Unique Endosomal/Lysosomal System of Giardia lamblia. In: Molecular Regulation of Endocytosis. InTech; 2012. doi:10.5772/45786.

Abodeely M, Dubois KN, Hehl A, Stefanie S, Sajid M, Desouza W, et al. A contiguous compartment functions as endoplasmic reticulum and endosome/lysosome in Giardia lamblia. Eukaryot Cell. 2009;8(11):1665–1676. doi: 10.1128/EC.00123-09. PubMed DOI PMC

Gadelha APR, Benchimol M, Souza W de. The cytoskeleton of Giardia intestinalis. In: Current Topics in Giardiasis. InTech; 2017. doi:10.5772/intechopen.70243, The Cytoskeleton of Giardia intestinalis.

Benchimol M, Piva B, Campanati L, De Souza W. Visualization of the funis of Giardia lamblia by high-resolution field emission scanning electron microscopy - New insights. J Struct Biol. 2004;147(2):102–115. doi: 10.1016/j.jsb.2004.01.017. PubMed DOI

Markova K, Uzlikova M, Tumova P, Jirakova K, Hagen G, Kulda J, Nohynkova E. Absence of a conventional spindle mitotic checkpoint in the binucleated single-celled parasite Giardia intestinalis. Eur J Cell Biol. 2016;95(10):355–367. doi: 10.1016/j.ejcb.2016.07.003. PubMed DOI

Sagan L. On the origin of mitosing cells. J Theor Biol. 1967;14(3):255–274. doi: 10.1016/0022-5193(67)90079-3. PubMed DOI

Schatz G, Haslbrunner E, Tuppy H. Deoxyribonucleic acid associated with yeast mitochondria. Biochem Biophys Res Commun. 1964;15(2):127–132. doi: 10.1016/0006-291X(64)90311-0. PubMed DOI

Dorn GW. Evolving concepts of mitochondrial dynamics. Annu Rev Physiol. 2019;81(1):1–17. doi: 10.1146/annurev-physiol-020518-114358. PubMed DOI

Okamoto K, Shaw JM. Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu Rev Genet. 2005;39(1):503–536. doi: 10.1146/annurev.genet.38.072902.093019. PubMed DOI

Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148(6):1145–1159. doi: 10.1016/j.cell.2012.02.035. PubMed DOI PMC

Chan DC. Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol Mech Dis. 2020;15(1):235–259. doi: 10.1146/annurev-pathmechdis-012419-032711. PubMed DOI

Suárez-Rivero J, Villanueva-Paz M, de la Cruz-Ojeda P, de la Mata M, Cotán D, Oropesa-Ávila M, de Lavera I, Álvarez-Córdoba M, Luzón-Hidalgo R, Sánchez-Alcázar J. Mitochondrial dynamics in mitochondrial diseases. Diseases. 2016;5(1):1. doi: 10.3390/diseases5010001. PubMed DOI PMC

Lewis SC, Uchiyama LF, Nunnari J. ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells. Science. 2016;353:af5549. doi: 10.1126/science.aaf5549. PubMed DOI PMC

Korobova F, Ramabhadran V, Higgs HN. An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2. Science. 2013;339(6118):464–467. doi: 10.1126/science.1228360. PubMed DOI PMC

Taguchi N, Ishihara N, Jofuku A, Oka T, Mihara K. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem. 2007;282(15):11521–11529. doi: 10.1074/jbc.M607279200. PubMed DOI

Park YY, Cho H. Mitofusin 1 is degraded at G2/M phase through ubiquitylation by MARCH5. Cell Div. 2012;7(1):25. doi: 10.1186/1747-1028-7-25. PubMed DOI PMC

Melo EJL, Attias M, De Souza W. The single mitochondrion of tachyzoites of Toxoplasma gondii. J Struct Biol. 2000;130(1):27–33. doi: 10.1006/jsbi.2000.4228. PubMed DOI

Kobayashi T, Sato S, Takamiya S, Komaki-Yasuda K, Yano K, Hirata A, Onitsuka I, Hata M, Mi-ichi F, Tanaka T, Hase T, Miyajima A, Kawazu SI, Watanabe YI, Kita K. Mitochondria and apicoplast of Plasmodium falciparum: behaviour on subcellular fractionation and the implication. Mitochondrion. 2007;7(1-2):125–132. doi: 10.1016/j.mito.2006.11.021. PubMed DOI

Frénal K, Jacot D, Hammoudi PM, Graindorge A, MacO B, Soldati-Favre D. Myosin-dependent cell-cell communication controls synchronicity of division in acute and chronic stages of Toxoplasma gondii. Nat Commun. 2017;8(1). 10.1038/ncomms15710. PubMed PMC

Lacomble S, Vaughan S, Gadelha C, Morphew MK, Shaw MK, McIntosh JR, et al. Three-dimensional cellular architecture of the flagellar pocket and associated cytoskeleton in trypanosomes revealed by electron microscope tomography. J Cell Sci. 2009;122(8):1081–1090. doi: 10.1242/jcs.045740. PubMed DOI PMC

Francia ME, Striepen B. Cell division in apicomplexan parasites. Nature Reviews Microbiology. 2014;12(2):125–136. doi: 10.1038/nrmicro3184. PubMed DOI

Burki F, Roger AJ, Brown MW, Simpson AGB. The new tree of eukaryotes. Trends Ecol Evol. 2020;35(1):43–55. doi: 10.1016/j.tree.2019.08.008. PubMed DOI

Leger MM, Kolisko M, Kamikawa R, Stairs CW, Kume K, Čepička I, Silberman JD, Andersson JO, Xu F, Yabuki A, Eme L, Zhang Q, Takishita K, Inagaki Y, Simpson AGB, Hashimoto T, Roger AJ. Organelles that illuminate the origins of Trichomonas hydrogenosomes and Giardia mitosomes. Nat Ecol Evol. 2017;1(4):0092. doi: 10.1038/s41559-017-0092. PubMed DOI PMC

Xu F, Jerlström-Hultqvist J, Kolisko M, Simpson AGB, Roger AJ, Svärd SG, Andersson JO. On the reversibility of parasitism: adaptation to a free-living lifestyle via gene acquisitions in the diplomonad Trepomonas sp. PC1. BMC Biol. 2016;14(1):62. doi: 10.1186/s12915-016-0284-z. PubMed DOI PMC

Benchimol M, Engelke F. Hydrogenosome behavior during the cell cycle in Tritrichomonas foetus. Biol Cell. 2003;95(5):283–293. doi: 10.1016/S0248-4900(03)00060-1. PubMed DOI

Park JS, Kolisko M, Heiss AA, Simpson AGB. Light microscopic observations, ultrastructure, and molecular phylogeny of Hicanonectes teleskopos n. g., n. sp., a deep-branching relative of diplomonads. J Eukaryot Microbiol. 2009;56(4):373–384. doi: 10.1111/j.1550-7408.2009.00412.x. PubMed DOI

Yubuki N, Huang SSC, Leander BS. Comparative ultrastructure of fornicate excavates, including a novel free-living relative of diplomonads: Aduncisulcus paluster gen. et sp. nov. Protist. 2016;167(6):584–596. doi: 10.1016/j.protis.2016.10.001. PubMed DOI

Kulda J, Nohýnková E. Flagellates of the human intestine and of intestines of other species. In: Kreier JP, editor. Parasitic Protozoa. Volume 2. Academ Press; 1978. p. 2–139.

Brugerolle G, Joyon L, Oktem N. Contribution à l’étude cytologique et phylétique des diplozoaires (Zoomastigophorea, Diplozoa, Dangeard 1910). VI. Caractères généraux des. Protistologica. 1975;9:495–502. https://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=PASCAL7650006905. Accessed 17 Aug 2020.

Leger MM, Kolísko M, Stairs CW, Simpson AGB. Mitochondrion-related organelles in free-living protists. In: Tachezy J, editor. Hydrogenosomes and Mitosomes: Mitochondria of Anaerobic Eukaryotes. Microbiology Monographs. 2019. p. 287–308.

Santos HJ, Makiuchi T, Nozaki T. Reinventing an organelle: the reduced mitochondrion in parasitic protists. Trends Parasitol. 2018;34(12):1038–1055. doi: 10.1016/j.pt.2018.08.008. PubMed DOI

Dolezal P, Dancis A, Lesuisse E, Sutak R, Hrdý I, Embley TM, et al. Frataxin, a conserved mitochondrial protein, in the hydrogenosome of Trichomonas vaginalis. Eukaryot Cell. 2007;6(8):1431–1438. doi: 10.1128/EC.00027-07. PubMed DOI PMC

Füssy Z, Vinopalová M, Treitli SC, Pánek T, Smejkalová P, Čepička I, Doležal P, Hampl V. Retortamonads from vertebrate hosts share features of anaerobic metabolism and pre-adaptations to parasitism with diplomonads. Parasitol Int. 2021;82:102308. doi: 10.1016/j.parint.2021.102308. PubMed DOI PMC

Tängemo C, Ronchi P, Colombelli J, Haselmann U, Simpson JC, Antony C, Stelzer EHK, Pepperkok R, Reynaud EG. A novel laser nanosurgery approach supports de novo Golgi biogenesis in mammalian cells. J Cell Sci. 2011;124(6):978–987. doi: 10.1242/jcs.079640. PubMed DOI

Tachezy J, Sánchez LB, Müller M. Mitochondrial type iron-sulfur cluster assembly in the amitochondriate eukaryotes Trichomonas vaginalis and Giardia intestinalis, as indicated by the phylogeny of IscS. Mol Biol Evol. 2001;18:1919–1928. http://www.ncbi.nlm.nih.gov/pubmed/11557797. Accessed 18 Dec 2014, 10, DOI: 10.1093/oxfordjournals.molbev.a003732. PubMed

Dolezal P, Smíd O, Rada P, Zubácová Z, Bursać D, Suták R, et al. Giardia mitosomes and trichomonad hydrogenosomes share a common mode of protein targeting. Proc Natl Acad Sci U S A. 2005;102(31):10924–10929. doi: 10.1073/pnas.0500349102. PubMed DOI PMC

Dawson SC, House SA. Life with eight flagella: flagellar assembly and division in Giardia. Current Opinion in Microbiology. 2010;13(4):480–490. doi: 10.1016/j.mib.2010.05.014. PubMed DOI PMC

Feely DE, Holberton D V., Erlandsen SL. The biology of Giardia. Giardiasis. 1990;:11–49.

Nosala C, Hagen KD, Dawson SC. ‘Disc-o-fever’: getting down with Giardia”</i>s groovy microtubule organelle. Trends Cell Biol. 2018;28:99–112. doi:10.1016/j.tcb.2017.10.007, 2. PubMed PMC

Tůmová P, Kulda J, Nohýnková E. Cell division of Giardia intestinalis: assembly and disassembly of the adhesive disc, and the cytokinesis. Cell Motil Cytoskeleton. 2007;64(4):288–298. doi: 10.1002/cm.20183. PubMed DOI

Hardin WR, Li R, Xu J, Shelton AM, Alas GCM, Minin VN, Paredez AR. Myosin-independent cytokinesis in Giardia utilizes flagella to coordinate force generation and direct membrane trafficking. Proc Natl Acad Sci U S A. 2017;114(29):E5854–E5863. doi: 10.1073/pnas.1705096114. PubMed DOI PMC

Jedelský PL, Doležal P, Rada P, Pyrih J, Smíd O, Hrdý I, et al. The minimal proteome in the reduced mitochondrion of the parasitic protist Giardia intestinalis. PLoS One. 2011;6(2):e17285. doi: 10.1371/journal.pone.0017285. PubMed DOI PMC

Hennessey KM, Alas GCM, Rogiers I, Li R, Merritt EA, Paredez AR. Nek8445, a protein kinase required for microtubule regulation and cytokinesis in Giardia lamblia. Mol Biol Cell. 2020;31(15):1611–1622. doi: 10.1091/mbc.E19-07-0406. PubMed DOI PMC

Kolisko M, Silberman JD, Cepicka I, Yubuki N, Takishita K, Yabuki A, Leander BS, Inouye I, Inagaki Y, Roger AJ, Simpson AGB. A wide diversity of previously undetected free-living relatives of diplomonads isolated from marine/saline habitats. Environ Microbiol. 2010;12:2700–2710. doi: 10.1111/j.1462-2920.2010.02239.x. PubMed DOI

Mai Z, Ghosh S, Frisardi M, Rosenthal B, Rogers R, Samuelson J. Hsp60 is targeted to a cryptic mitochondrion-derived organelle in the microaerophilic protozoan parasite Entamoeba histolytica. Mol Cell Biol. 1999;19:2198–2205. http://www.ncbi.nlm.nih.gov/pubmed/10022906. Accessed 3 Aug 2018, 3, DOI: 10.1128/MCB.19.3.2198. PubMed PMC

Benchimol M. Hydrogenosomes under microscopy. Tissue Cell. 2009;41(3):151–168. doi: 10.1016/j.tice.2009.01.001. PubMed DOI

Voeltz GK, Prinz WA. Sheets, ribbons and tubules - how organelles get their shape. Nat Rev Mol Cell Biol. 2007;8(3):258–264. doi: 10.1038/nrm2119. PubMed DOI

Faelber K, Dietrich L, Noel JK, Wollweber F, Pfitzner AK, Mühleip A, Sánchez R, Kudryashev M, Chiaruttini N, Lilie H, Schlegel J, Rosenbaum E, Hessenberger M, Matthaeus C, Kunz S, von der Malsburg A, Noé F, Roux A, van der Laan M, Kühlbrandt W, Daumke O. Structure and assembly of the mitochondrial membrane remodelling GTPase Mgm1. Nature. 2019;571(7765):429–433. doi: 10.1038/s41586-019-1372-3. PubMed DOI PMC

Kondadi AK, Anand R, Hänsch S, Urbach J, Zobel T, Wolf DM, et al. Cristae undergo continuous cycles of membrane remodelling in a MICOS-dependent manner. EMBO Rep. 2020;21. doi:10.15252/embr.201949776. PubMed PMC

Paumard P, Vaillier J, Coulary B, Schaeffer J, Soubannier V, Mueller DM, Brèthes D, di Rago JP, Velours J. The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J. 2002;21(3):221–230. doi: 10.1093/emboj/21.3.221. PubMed DOI PMC

Visser W, van Spronsen EA, Nanninga N, Pronk JT, Gijs Kuenen J, van Dijken JP. Effects of growth conditions on mitochondrial morphology in Saccharomyces cerevisiae. Antonie Van Leeuwenhoek. 1995;67(3):243–253. doi: 10.1007/bf00873688. PubMed DOI

Posakony JW, England JM, Attardi G. Mitochondrial growth and division during the cell cycle in HeLa cells. J Cell Biol. 1977;74(2):468–491. doi: 10.1083/jcb.74.2.468. PubMed DOI PMC

Anastacio MM, Kanter EM, Makepeace CM, Keith AD, Zhang H, Schuessler RB, et al. Relationship between mitochondrial matrix volume and cellular volume in response to stress and the role of atp-sensitive potassium channel. Circulation. 2013;128 SUPPL.1. PubMed PMC

Keister DB. Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile. Trans R Soc Trop Med Hyg. 1983;77:487–488. http://www.ncbi.nlm.nih.gov/pubmed/6636276. Accessed 21 Feb 2015, 4, DOI: 10.1016/0035-9203(83)90120-7. PubMed

Lauwaet T, Davids BJ, Torres-Escobar A, Birkeland SR, Cipriano MJ, Preheim SP, Palm D, Svärd SG, McArthur AG, Gillin FD. Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation. Mol Biochem Parasitol. 2007;152(1):80–89. doi: 10.1016/j.molbiopara.2006.12.001. PubMed DOI PMC

Martincová E, Voleman L, Pyrih J, Žárský V, Vondráčková P, Kolísko M, Tachezy J, Doležal P. Probing the biology of Giardia intestinalis mitosomes using in vivo enzymatic tagging. Mol Cell Biol. 2015;35(16):2864–2874. doi: 10.1128/MCB.00448-15. PubMed DOI PMC

Efficient CRISPR/Cas9-mediated gene disruption in the tetraploid protist Giardia intestinalis

The Giardia ventrolateral flange is a lamellar membrane protrusion that supports attachment