Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria

Cell Mol Life Sci. 2019 May;76(9):1759-1777. doi: 10.1007/s00018-019-03039-y. Epub 2019 Feb 14.


Oxygen is required for the survival of the majority of eukaryotic organisms, as it is important for many cellular processes. Eukaryotic cells utilize oxygen for the production of biochemical energy in the form of adenosine triphosphate (ATP) generated from the catabolism of carbon-rich fuels such as glucose, lipids and glutamine. The intracellular sites of oxygen consumption-coupled ATP production are the mitochondria, double-membraned organelles that provide a dynamic and multifaceted role in cell signalling and metabolism. Highly evolutionarily conserved molecular mechanisms exist to sense and respond to changes in cellular oxygen levels. The primary transcriptional regulators of the response to decreased oxygen levels (hypoxia) are the hypoxia-inducible factors (HIFs), which play important roles in both physiological and pathophysiological contexts. In this review we explore the relationship between HIF-regulated signalling pathways and the mitochondria, including the regulation of mitochondrial metabolism, biogenesis and distribution.

Keywords: HIF; Hypoxia; Metabolism; Mitochondrial biogenesis; Oxphos; Oxygen; Respiratory chain.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Hypoxia / physiology*
  • Electron Transport / physiology
  • Energy Metabolism / physiology*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Mitochondria / metabolism*
  • Oxygen / metabolism*
  • Oxygen Consumption / physiology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction


  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • Oxygen