Mitonuclear communication in homeostasis and stress

Nat Rev Mol Cell Biol. 2016 Apr;17(4):213-26. doi: 10.1038/nrm.2016.23. Epub 2016 Mar 9.


Mitochondria participate in crucial cellular processes such as energy harvesting and intermediate metabolism. Although mitochondria possess their own genome--a vestige of their bacterial origins and endosymbiotic evolution--most mitochondrial proteins are encoded in the nucleus. The expression of the mitochondrial proteome hence requires tight coordination between the two genomes to adapt mitochondrial function to the ever-changing cellular milieu. In this Review, we focus on the pathways that coordinate the communication between mitochondria and the nucleus during homeostasis and mitochondrial stress. These pathways include nucleus-to-mitochondria (anterograde) and mitochondria-to-nucleus (retrograde) communication, mitonuclear feedback signalling and proteostasis regulation, the integrated stress response and non-cell-autonomous communication. We discuss how mitonuclear communication safeguards cellular and organismal fitness and regulates lifespan.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Communication
  • Cell Nucleus / physiology*
  • Homeostasis*
  • Mitochondria / physiology*
  • Mitochondrial Proteins / metabolism
  • Models, Biological
  • Signal Transduction
  • Stress, Physiological*


  • Mitochondrial Proteins