Presence of a Member of the Mitochondrial Carrier Family in Hydrogenosomes: Conservation of Membrane-Targeting Pathways between Hydrogenosomes and Mitochondria

Abstract

A number of microaerophilic eukaryotes lack mitochondria but possess another organelle involved in energy metabolism, the hydrogenosome. Limited phylogenetic analyses of nuclear genes support a common origin for these two organelles. We have identified a protein of the mitochondrial carrier family in the hydrogenosome of Trichomonas vaginalis and have shown that this protein, Hmp31, is phylogenetically related to the mitochondrial ADP-ATP carrier (AAC). We demonstrate that the hydrogenosomal AAC can be targeted to the inner membrane of mitochondria isolated from Saccharomyces cerevisiae through the Tim9-Tim10 import pathway used for the assembly of mitochondrial carrier proteins. Conversely, yeast mitochondrial AAC can be targeted into the membranes of hydrogenosomes. The hydrogenosomal AAC contains a cleavable, N-terminal presequence; however, this sequence is not necessary for targeting the protein to the organelle. These data indicate that the membrane-targeting signal(s) for hydrogenosomal AAC is internal, similar to that found for mitochondrial carrier proteins. Our findings indicate that the membrane carriers and membrane protein-targeting machinery of hydrogenosomes and mitochondria have a common evolutionary origin. Together, they provide strong evidence that a single endosymbiont evolved into a progenitor organelle in early eukaryotic cells that ultimately give rise to these two distinct organelles and support the hydrogen hypothesis for the origin of the eukaryotic cell.

ACKNOWLEDGMENTS

We thank Miriam Makabi for technical assistance, Harry Hahn for help with the phylogeny programs, and Gottfried Schatz, James Lake, Alexander van der Bliek, and members of our laboratory for helpful advice and critical comments on the manuscript.

This work was supported by National Institutes of Health grant AI27857 to P.J.J., postdoctoral fellowships from the Damon Runyon-Walter Winchell Cancer Research Foundation and the National Science Foundation to C.M.K. and from the Deutsche Forschungsgemeinschaft to E.P., and a predoctoral training grant (NIH AI07323) to P.J.B. P.J.J. is a recipient of a Burroughs-Wellcome Scholar in Molecular Parasitology award.