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Synchronized Mitochondrial and Cytosolic Translation Programs

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Journal Nature
Specialty Science
Date 2016 May 27
PMID 27225121
Citations 165
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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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References
1.
Poyton R, Bellus G, McKee E, Sevarino K, Goehring B . In organello mitochondrial protein and RNA synthesis systems from Saccharomyces cerevisiae. Methods Enzymol. 1996; 264:36-42. DOI: 10.1016/s0076-6879(96)64006-3. View

2.
Ingolia N, Ghaemmaghami S, Newman J, Weissman J . Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science. 2009; 324(5924):218-23. PMC: 2746483. DOI: 10.1126/science.1168978. View

3.
Eisen M, Spellman P, Brown P, Botstein D . Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998; 95(25):14863-8. PMC: 24541. DOI: 10.1073/pnas.95.25.14863. View

4.
Baruffini E, Lodi T, Dallabona C, Foury F . A single nucleotide polymorphism in the DNA polymerase gamma gene of Saccharomyces cerevisiae laboratory strains is responsible for increased mitochondrial DNA mutability. Genetics. 2007; 177(2):1227-31. PMC: 2034627. DOI: 10.1534/genetics.107.079293. View

5.
Gruschke S, Rompler K, Hildenbeutel M, Kehrein K, Kuhl I, Bonnefoy N . The Cbp3-Cbp6 complex coordinates cytochrome b synthesis with bc(1) complex assembly in yeast mitochondria. J Cell Biol. 2012; 199(1):137-50. PMC: 3461508. DOI: 10.1083/jcb.201206040. View