Mitochondria are archetypal organelles of endosymbiotic origin in eukaryotic cells. Some unicellular eukaryotes (protists) were considered to be primarily amitochondrial organisms that diverged from the eukaryotic lineage before the acquisition of the premitochondrial endosymbiont, but their amitochondrial status was recently challenged by the discovery of mitochondria-like double membrane-bound organelles called mitosomes. Here, we report that proteins targeted into mitosomes of Giardia intestinalis have targeting signals necessary and sufficient to be recognized by the mitosomal protein import machinery. Expression of these mitosomal proteins in Trichomonas vaginalis results in targeting to hydrogenosomes, a hydrogen-producing form of mitochondria. We identify, in Giardia and Trichomonas, proteins related to the component of the translocase in the inner membrane from mitochondria and the processing peptidase. A shared mode of protein targeting supports the hypothesis that mitosomes, hydrogenosomes, and mitochondria represent different forms of the same fundamental organelle having evolved under distinct selection pressures.

Department of Parasitology Charles University Vinicna 7 128 44 Prague 2 Czech Republic

See more in PubMed

Tovar, J., Fischer, A. & Clark, C. G. (1999) Mol. Microbiol. 32, 1013-1021. PubMed

Mai, Z., Ghosh, S., Frisardi, M., Rosenthal, B., Rogers, R. & Samuelson, J. (1999) Mol. Cell. Biol. 19, 2198-2205. PubMed PMC

Williams, B. A., Hirt, R. P., Lucocq, J. M. & Embley, T. M. (2002) Nature 418, 865-869. PubMed

Tovar, J., Leon-Avila, G., Sánchez, L. B., Sutak, R., Tachezy, J., van der Giezen, M., Hernandez, M., Müller, M. & Lucocq, J. M. (2003) Nature 426, 172-176. PubMed

Adam, R. D. (2001) Clin. Microbiol. Rev. 14, 447-475. PubMed PMC

Best, A. A., Morrison, H. G., McArthur, A. G., Sogin, M. L. & Olsen, G. J. (2004) Genome Res. 14, 1537-1547. PubMed PMC

Cavalier-Smith, T. (1987) Cold Spring Harbor Symp. Quant. Biol. 52, 805-824. PubMed

Hashimoto, T., Sanchez, L. B., Shirakura, T., Müller, M. & Hasegawa, M. (1998) Proc. Natl. Acad. Sci. USA 95, 6860-6865. PubMed PMC

Roger, A. J., Svard, S. G., Tovar, J., Clark, C. G., Smith, M. W., Gillin, F. D. & Sogin, M. L. (1998) Proc. Natl. Acad. Sci. USA 95, 229-234. PubMed PMC

Tachezy, J., Sanchez, L. B. & Müller, M. (2001) Mol. Biol. Evol. 18, 1919-1928. PubMed

Lill, R. & Kispal, G. (2000) Trends Biochem. Sci. 25, 352-356. PubMed

Sutak, R., Dolezal, P., Fiumera, H. L., Hrdy, I., Dancis, A., Delgadillo-Correa, M., Johnson, P. J., Müller, M. & Tachezy, J. (2004) Proc. Natl. Acad. Sci. USA 101, 10368-10373. PubMed PMC

Pilon-Smits, E. A., Garifullina, G. F., Abdel-Ghany, S., Kato, S., Mihara, H., Hale, K. L., Burkhead, J. L., Esaki, N., Kurihara, T. & Pilon, M. (2002) Plant Physiol. 130, 1309-1318. PubMed PMC

Emelyanov, V. V. (2003) FEMS Microbiol. Lett. 226, 257-266. PubMed

Dyall, S. D., Brown, M. T. & Johnson, P. J. (2004) Science 304, 253-257. PubMed

van der Giezen, M., Slotboom, D. J., Horner, D. S., Dyal, P. L., Harding, M., Xue, G. P., Embley, T. M. & Kunji, E. R. (2002) EMBO J. 21, 572-579. PubMed PMC

Emelyanov, V. V. (2001) FEBS Lett. 501, 11-18. PubMed

Neupert, W. (1997) Annu. Rev. Biochem. 66, 863-917. PubMed

Rehling, P., Wiedemann, N., Pfanner, N. & Truscott, K. N. (2001) Crit. Rev. Biochem. Mol. Biol. 36, 291-336. PubMed

Truscott, K. N., Voos, W., Frazier, A. E., Lind, M., Li, Y., Geissler, A., Dudek, J., Muller, H., Sickmann, A., Meyer, H. E., et al. (2003) J. Cell Biol. 163, 707-713. PubMed PMC

Mokranjac, D., Sichting, M., Neupert, W. & Hell, K. (2003) EMBO J. 22, 4945-4956. PubMed PMC

Gakh, O., Cavadini, P. & Isaya, G. (2002) Biochim. Biophys. Acta 1592, 63-77. PubMed

Bradley, P. J., Lahti, C. J., Plümper, E. & Johnson, P. J. (1997) EMBO J. 16, 3484-3493. PubMed PMC

Nixon, J. E., Wang, A., Field, J., Morrison, H. G., McArthur, A. G., Sogin, M. L., Loftus, B. J. & Samuelson, J. (2002) Eukaryotic Cell 1, 181-190. PubMed PMC

Keister, D. B. (1983) Trans. R. Soc. Trop. Med. Hyg. 77, 487-488. PubMed

Diamond, L. S. (1957) J. Parasitol. 43, 488-490. PubMed

Sun, C. H., Chou, C. F. & Tai, J. H. (1998) Mol. Biochem. Parasitol. 92, 123-132. PubMed

Hrdy, I., Hirt, R. P., Dolezal, P., Bardonova, L., Foster, P. G., Tachezy, J. & Embley, T. M. (2004) Nature 432, 618-622. PubMed

Macasev, D., Whelan, J., Newbigin, E., Silva-Filho, M. C., Mulhern, T. D. & Lithgow, T. (2004) Mol. Biol. Evol. 21, 1557-1564. PubMed

Drmota, T., Proost, P., Van Ranst, M., Weyda, F., Kulda, J. & Tachezy, J. (1996) Mol. Biochem. Parasitol. 83, 221-234. PubMed

Murakami, H., Pain, D. & Blobel, G. (1988) J. Cell Biol. 107, 2051-2057. PubMed PMC

Tokuyasu, K. T. (1981) J. Electron Microsc. 30, 93-94.

Adamec, J., Gakh, O., Spizek, J. & Kalousek, F. (1999) Arch. Biochem. Biophys. 370, 77-85. PubMed

Mühlenhoff, U., Richhardt, N., Gerber, J. & Lill, R. (2002) J. Biol. Chem. 277, 29810-29816. PubMed

Mühlenhoff, U., Balk, J., Richhardt, N., Kaiser, J. T., Sipos, K., Kispal, G. & Lill, R. (2004) J. Biol. Chem. 279, 36906-36915. PubMed

Cserzo, M., Wallin, E., Simon, I., von Heijne, G. & Elofsson, A. (1997) Protein Eng. 10, 673-676. PubMed

Walsh, P., Bursac, D., Law, Y. C., Cyr, D. & Lithgow, T. (2004) EMBO Rep. 5, 567-571. PubMed PMC

Embley, T. M., van der Giezen, M., Horner, D. S., Dyal, P. L., Bell, S. & Foster, P. G. (2003) IUBMB Life 55, 387-395. PubMed

Likic, V. A., Perry, A., Hulett, J., Derby, M., Traven, A., Waller, R. F., Keeling, P. J., Koehler, C. M., Curran, S. P., Gooley, P. R., et al. (2005) J. Mol. Biol. 347, 81-93. PubMed

Herrmann, J. M. (2003) Trends Microbiol. 11, 74-79. PubMed

Martin, W. & Russell, M. J. (2003) Philos. Trans. R. Soc. Lond., B, Biol. Sci. 358, 59-83. PubMed PMC

Mlf mediates proteotoxic response via formation of cellular foci for protein folding and degradation in Giardia

A hybrid TIM complex mediates protein import into hydrogenosomes of Trichomonas vaginalis

Adaptation of the late ISC pathway in the anaerobic mitochondrial organelles of Giardia intestinalis

A mitochondrion-free eukaryote contains proteins capable of import into an exogenous mitochondrion-related organelle

Structurally derived universal mechanism for the catalytic cycle of the tail-anchored targeting factor Get3

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

Inheritance of the reduced mitochondria of Giardia intestinalis is coupled to the flagellar maturation cycle

The evolution of the Puf superfamily of proteins across the tree of eukaryotes

A Single Tim Translocase in the Mitosomes of Giardia intestinalis Illustrates Convergence of Protein Import Machines in Anaerobic Eukaryotes

Fe-S cluster assembly in the supergroup Excavata

Giardia intestinalis mitosomes undergo synchronized fission but not fusion and are constitutively associated with the endoplasmic reticulum

N-Terminal Presequence-Independent Import of Phosphofructokinase into Hydrogenosomes of Trichomonas vaginalis

Probing the Biology of Giardia intestinalis Mitosomes Using In Vivo Enzymatic Tagging

NIF-type iron-sulfur cluster assembly system is duplicated and distributed in the mitochondria and cytosol of Mastigamoeba balamuthi

Histone H3 Variants in Trichomonas vaginalis

Live imaging of mitosomes and hydrogenosomes by HaloTag technology

The core components of organelle biogenesis and membrane transport in the hydrogenosomes of Trichomonas vaginalis

The minimal proteome in the reduced mitochondrion of the parasitic protist Giardia intestinalis

The monothiol single-domain glutaredoxin is conserved in the highly reduced mitochondria of Giardia intestinalis

Flavodiiron protein from Trichomonas vaginalis hydrogenosomes: the terminal oxygen reductase