Article | Published:

Synchronized mitochondrial and cytosolic translation programs

Nature volume 533, pages 499503 (26 May 2016) | Download Citation

Abstract

Oxidative phosphorylation (OXPHOS) is a vital process for energy generation, and is carried out by complexes within the mitochondria. OXPHOS complexes pose a unique challenge for cells because their subunits are encoded on both the nuclear and the mitochondrial genomes. Genomic approaches designed to study nuclear/cytosolic and bacterial gene expression have not been broadly applied to mitochondria, so the co-regulation of OXPHOS genes remains largely unexplored. Here we monitor mitochondrial and nuclear gene expression in Saccharomyces cerevisiae during mitochondrial biogenesis, when OXPHOS complexes are synthesized. We show that nuclear- and mitochondrial-encoded OXPHOS transcript levels do not increase concordantly. Instead, mitochondrial and cytosolic translation are rapidly, dynamically and synchronously regulated. Furthermore, cytosolic translation processes control mitochondrial translation unidirectionally. Thus, the nuclear genome coordinates mitochondrial and cytosolic translation to orchestrate the timely synthesis of OXPHOS complexes, representing an unappreciated regulatory layer shaping the mitochondrial proteome. Our whole-cell genomic profiling approach establishes a foundation for studies of global gene regulation in mitochondria.

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All data are deposited in Gene Expression Omnibus (accession number GSE74454).

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Acknowledgements

We thank F. Winston, T. Fox, G. Brar and members of the Churchman lab for advice and discussions; members of the O’Shea, Novina, and Springer labs for use of equipment and advice; and M. Hickman and D. Botstein for sharing the HAP1+ strain. Research supported by a Damon Runyon Cancer Research Foundation Frey Award (to L.S.C.), a Burroughs Wellcome Fund Career Award at the Scientific Interface (to L.S.C.), an Ellison Medical Foundation New Scholar in Aging Award (to L.S.C.), the National Institutes of Health F32 (to M.T.C.), and a Boehringer Ingelheim Fonds PhD Fellowship (to G.S.).

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  1. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Mary T. Couvillion
    • , Iliana C. Soto
    • , Gergana Shipkovenska
    •  & L. Stirling Churchman

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Contributions

M.T.C. and L.S.C. designed the research and wrote the manuscript. M.T.C. conducted the experiments with help from I.C.S. who performed mitoribosome profiling with drug treatments, and G.S., who created and performed mitoribosome profiling on the pet111Δ strain. M.T.C. analysed the data. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to L. Stirling Churchman.

Reviewer Information Nature thanks P. Van Damme and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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https://doi.org/10.1038/nature18015

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