Synchronized mitochondrial and cytosolic translation programs

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. The genes encoding the subunits of oxidative phosphorylation complexes are split between the nuclear and mitochondrial genomes, but their translation is synchronized by signalling from the cytosol to the mitochondria. Aligning mitochondrial and nuclear expression The OXPHOS (oxidative phosphorylation) complexes within the mitochondrial inner membrane generate the large majority of the cell's energy through the synthesis of ATP from ADP and inorganic phosphate during the oxidation of NADH by molecular oxygen. As the OXPOS complex contains subunits encoded by both the nuclear and the mitochondrial genomes, it has been widely assumed that there must be communication between the two compartments to coordinate gene expression. Stirling Churchman and colleagues have now characterized synthesis of the OXPHOS subunits. They find that nuclear and mitochondrial transcription programs are independently regulated under the direction of the nuclear genome. Regulation occurs not at the level of transcription, but rather in terms of translation, with mitochondrial translation regulated through the cytosolic ribosomes.