Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways

Int J Mol Sci. 2020 May 28;21(11):3820. doi: 10.3390/ijms21113820.


The assembly of mitochondrial oxidative phosphorylation (OXPHOS) complexes is an intricate process, which-given their dual-genetic control-requires tight co-regulation of two evolutionarily distinct gene expression machineries. Moreover, fine-tuning protein synthesis to the nascent assembly of OXPHOS complexes requires regulatory mechanisms such as translational plasticity and translational activators that can coordinate mitochondrial translation with the import of nuclear-encoded mitochondrial proteins. The intricacy of OXPHOS complex biogenesis is further evidenced by the requirement of many tightly orchestrated steps and ancillary factors. Early-stage ancillary chaperones have essential roles in coordinating OXPHOS assembly, whilst late-stage assembly factors-also known as the LYRM (leucine-tyrosine-arginine motif) proteins-together with the mitochondrial acyl carrier protein (ACP)-regulate the incorporation and activation of late-incorporating OXPHOS subunits and/or co-factors. In this review, we describe recent discoveries providing insights into the mechanisms required for optimal OXPHOS biogenesis, including the coordination of mitochondrial gene expression with the availability of nuclear-encoded factors entering via mitochondrial protein import systems.

Keywords: LYRM proteins; OXPHOS assembly factors; OXPHOS biogenesis; mitochondrial ACP; mitochondrial gene expression; mitochondrial import.

Publication types

  • Review

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • DNA, Mitochondrial / metabolism
  • Electron Transport Complex IV / metabolism*
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Organelle Biogenesis*
  • Oxidative Phosphorylation*
  • Protein Biosynthesis
  • Protein Domains
  • Protein Transport*
  • Species Specificity
  • Transcriptional Activation*


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Nuclear Proteins
  • OXA1 protein
  • Electron Transport Complex IV