The energetic state of mitochondria modulates complex III biogenesis through the ATP-dependent activity of Bcs1

Cell Metab. 2013 Oct 1;18(4):567-77. doi: 10.1016/j.cmet.2013.08.017. Epub 2013 Sep 19.

Abstract

Our understanding of the mechanisms involved in mitochondrial biogenesis has continuously expanded during the last decades, yet little is known about how they are modulated to optimize the functioning of mitochondria. Here, we show that mutations in the ATP binding domain of Bcs1, a chaperone involved in the assembly of complex III, can be rescued by mutations that decrease the ATP hydrolytic activity of the ATP synthase. Our results reveal a Bcs1-mediated control loop in which the biogenesis of complex III is modulated by the energy-transducing activity of mitochondria. Although ATP is well known as a regulator of a number of cellular activities, we show here that ATP can be also used to modulate the biogenesis of an enzyme by controlling a specific chaperone involved in its assembly. Our study further highlights the intramitochondrial adenine nucleotide pool as a potential target for the treatment of Bcs1-based disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Synthetase Complexes / metabolism
  • Adenosine Triphosphate / pharmacology*
  • Electron Transport Complex III / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondria / drug effects*
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Mutation
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • BCS1 protein, S cerevisiae
  • Membrane Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate
  • ATP Synthetase Complexes
  • Electron Transport Complex III