Mitochondrial Protein Synthesis Adapts to Influx of Nuclear-Encoded Protein

Cell. 2016 Oct 6;167(2):471-483.e10. doi: 10.1016/j.cell.2016.09.003. Epub 2016 Sep 29.

Abstract

Mitochondrial ribosomes translate membrane integral core subunits of the oxidative phosphorylation system encoded by mtDNA. These translation products associate with nuclear-encoded, imported proteins to form enzyme complexes that produce ATP. Here, we show that human mitochondrial ribosomes display translational plasticity to cope with the supply of imported nuclear-encoded subunits. Ribosomes expressing mitochondrial-encoded COX1 mRNA selectively engage with cytochrome c oxidase assembly factors in the inner membrane. Assembly defects of the cytochrome c oxidase arrest mitochondrial translation in a ribosome nascent chain complex with a partially membrane-inserted COX1 translation product. This complex represents a primed state of the translation product that can be retrieved for assembly. These findings establish a mammalian translational plasticity pathway in mitochondria that enables adaptation of mitochondrial protein synthesis to the influx of nuclear-encoded subunits.

Keywords: C12ORF62; COX1; MITRAC; OXPHOS; assembly; cytochrome c oxidase; mitochondrial ribosome; mitochondrial translation; translation regulation; translational plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Line, Tumor
  • Cyclooxygenase 1 / biosynthesis
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism*
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / biosynthesis
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism*
  • HEK293 Cells
  • Humans
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondria / enzymology*
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Oxidative Phosphorylation
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Mitochondrial
  • Ribosomes / metabolism

Substances

  • COA3 protein, human
  • COX14 protein, human
  • DNA, Mitochondrial
  • Membrane Proteins
  • Mitochondrial Proteins
  • RNA, Messenger
  • RNA, Mitochondrial
  • mitochondrial messenger RNA
  • Cyclooxygenase 1
  • PTGS1 protein, human
  • Electron Transport Complex IV