The mitochondrial UPR: mechanisms, physiological functions and implications in ageing

Nat Rev Mol Cell Biol. 2018 Feb;19(2):109-120. doi: 10.1038/nrm.2017.110. Epub 2017 Nov 22.


Mitochondrial function declines during ageing owing to the accumulation of deleterious mitochondrial genomes and damage resulting from the localized generation of reactive oxygen species, both of which are often exacerbated in diseases such as Parkinson disease. Cells have several mechanisms to assess mitochondrial function and activate a transcriptional response known as the mitochondrial unfolded protein response (UPRmt) when mitochondrial integrity and function are impaired. The UPRmt promotes cell survival and the recovery of the mitochondrial network to ensure optimal cellular function. Recent insights into the regulation, mechanisms and functions of the UPRmt have uncovered important and complex links to ageing and ageing-associated diseases. In this Review, we discuss the signal transduction mechanisms that regulate the UPRmt and the physiological consequences of its activation that affect cellular and organismal health during ageing.

Publication types

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

MeSH terms

  • Aging / physiology
  • Animals
  • DNA, Mitochondrial / metabolism
  • Humans
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • Mitochondrial Diseases / pathology
  • Mitochondrial Proteins / genetics
  • Mutation / genetics
  • Parkinson Disease / physiopathology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Unfolded Protein Response / genetics*
  • Unfolded Protein Response / physiology*


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Reactive Oxygen Species