Synchronized mitochondrial and cytosolic translation programs controlled by the nuclear genome (gDNA)

Both nuclear genes (in genomic DNA; gDNA), and genes (mitochondrial DNA; mtDNA) in organelles called mitochondria, are involved in assembly of the cellular energy-producing machinery. RNA-translation programs that coordinate the two systems have now been identified. Oxidative phosphorylation (OXPHOS) is a vital process for energy generation in virtually all eukaryotes (diploid organisms that normally carry mitochondria in their cytoplasm). This “energy factory” carries out its functions by complexes exclusively within the mitochondria. OXPHOS complexes pose a unique challenge for cells, because their subunits are encoded by DNA located on both the nuclear (gDNA) and the mitochondrial (mtDNA) genomes of the cell.

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 poorly understood. Authors [attached pdf files] monitored nuclear and mitochondrial gene expression in yeast (Saccharomyces cerevisiae) during mitochondrial biogenesis, during the time when OXPHOS complexes are synthesized. They showed that gDNA- and mtDNA-encoded OXPHOS transcript levels (DNA transcribed to RNA) do not increase concordantly. Instead, mitochondrial and cytosolic translation (of the messenger RNA into proteins) is (rapidly, dynamically and synchronously) regulated.

Furthermore, authors found that the cytosolic translation processes control mitochondrial translation uni-directionally––i.e. the nuclear genome coordinates mitochondrial, and cytosolic, translation to orchestrate the timely synthesis of OXPHOS complexes, representing an unappreciated regulatory layer that shapes the mitochondrial proteome. This interesting whole-cell genomic profiling approach (looking concomitantly at gDNA and mtDNA transcription) establishes a foundation for studies of global gene regulation in mitochondria.

Nature  26 May 2o16; 533: 499 – 503  and ‘News & Views” editorial, pp 472-473

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