Synchronized mitochondrial and cytosolic translation programs

Mary T. Couvillion, Iliana C. Soto, Gergana Shipkovenska and L. Stirling Churchman ()
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Mary T. Couvillion: Harvard Medical School
Iliana C. Soto: Harvard Medical School
Gergana Shipkovenska: Harvard Medical School
L. Stirling Churchman: Harvard Medical School

Nature, 2016, vol. 533, issue 7604, 499-503

Abstract: 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.

Date: 2016
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DOI: 10.1038/nature18015

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