Targeting and plasticity of mitochondrial proteins revealed by proximity-specific ribosome profiling.
Nearly all mitochondrial proteins are nuclear-encoded and are targeted to their mitochondrial destination from the cytosol. Here, we used proximity-specific ribosome profiling to comprehensively measure translation at the mitochondrial surface in yeast. Most inner-membrane proteins were cotranslationally targeted to mitochondria, reminiscent of proteins entering the endoplasmic reticulum (ER). Comparison between mitochondrial and ER localization demonstrated that the vast majority of proteins were targeted to a specific organelle. A prominent exception was the fumarate reductase Osm1, known to reside in mitochondria. We identified a conserved ER isoform of Osm1, which contributes to the oxidative protein-folding capacity of the organelle. This dual localization was enabled by alternative translation initiation sites encoding distinct targeting signals. These findings highlight the exquisite in vivo specificity of organellar targeting mechanisms.
These authors contributed equally to this work.
Christopher C
CC
Williams
These authors contributed equally to this work.
Calvin H
CH
Jan
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. These authors contributed equally to this work. jonathan.weissman@ucsf.edu.
Jonathan S
JS
Weissman
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational; D017510:Protein Folding; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
D024101:Mitochondrial Proteins; C063916:OSM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013385:Succinate Dehydrogenase