Regulation of mitochondrial structure and function by the F1Fo-ATPase inhibitor protein, IF1

Cell Metab. 2008 Jul;8(1):13-25. doi: 10.1016/j.cmet.2008.06.001.


When mitochondrial respiration is compromised, the F(1)F(o)-ATP synthase reverses and consumes ATP, serving to maintain the mitochondrial membrane potential (Delta psi(m)). This process is mitigated by IF(1). As little is known of the cell biology of IF(1), we have investigated the functional consequences of varying IF(1) expression. We report that, (1) during inhibition of respiration, IF(1) conserves ATP at the expense of Delta psi(m); (2) overexpression of IF(1) is protective against ischemic injury; (3) relative IF(1) expression level varies between tissues and cell types and dictates the response to inhibition of mitochondrial respiration; (4) the density of mitochondrial cristae is increased by IF(1) overexpression and decreased by IF(1) suppression; and (5) IF(1) overexpression increases the formation of dimeric ATP synthase complexes and increases F(1)F(o)-ATP synthase activity. Thus, IF(1) regulates mitochondrial function and structure under both physiological and pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Respiration
  • Gene Expression Regulation
  • Membrane Potential, Mitochondrial
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / physiology*
  • Mitochondria, Heart / ultrastructure
  • Proteins / physiology*
  • Proton-Translocating ATPases / antagonists & inhibitors*
  • Rats


  • ATPase inhibitory protein
  • Proteins
  • Adenosine Triphosphate
  • Proton-Translocating ATPases