Maintenance and Expression of Mammalian Mitochondrial DNA

Annu Rev Biochem. 2016 Jun 2;85:133-60. doi: 10.1146/annurev-biochem-060815-014402. Epub 2016 Mar 24.


Mammalian mitochondrial DNA (mtDNA) encodes 13 proteins that are essential for the function of the oxidative phosphorylation system, which is composed of four respiratory-chain complexes and adenosine triphosphate (ATP) synthase. Remarkably, the maintenance and expression of mtDNA depend on the mitochondrial import of hundreds of nuclear-encoded proteins that control genome maintenance, replication, transcription, RNA maturation, and mitochondrial translation. The importance of this complex regulatory system is underscored by the identification of numerous mutations of nuclear genes that impair mtDNA maintenance and expression at different levels, causing human mitochondrial diseases with pleiotropic clinical manifestations. The basic scientific understanding of the mechanisms controlling mtDNA function has progressed considerably during the past few years, thanks to advances in biochemistry, genetics, and structural biology. The challenges for the future will be to understand how mtDNA maintenance and expression are regulated and to what extent direct intramitochondrial cross talk between different processes, such as transcription and translation, is important.

Keywords: mitochondria; mtDNA; polymerase; replication; respiratory chain; transcription.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Evolution
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • DNA Replication
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Electron Transport / genetics
  • Gene Expression Regulation
  • Mammals
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Ribosomes / chemistry
  • Mitochondrial Ribosomes / metabolism
  • Models, Molecular
  • Oxidative Phosphorylation
  • Protein Biosynthesis*
  • Protein Transport
  • Signal Transduction
  • Transcription, Genetic*


  • DNA, Mitochondrial
  • Mitochondrial Proteins