Mitochondrial ATP synthase levels in brown adipose tissue are governed by the c-Fo subunit P1 isoform

FASEB J. 2008 Jan;22(1):55-63. doi: 10.1096/fj.07-8581com. Epub 2007 Jul 31.


Despite the significance of mitochondrial ATP synthase for mammalian metabolism, the regulation of the amount of ATP synthase in mammalian systems is not understood. As brown adipose tissue mitochondria contain very low amounts of ATP synthase, relative to respiratory chain components, they constitute a physiological system that allows for examination of the control of ATP synthase assembly. To examine the role of the expression of the P1-isoform of the c-Fo subunit in the biogenesis of ATP synthase, we made transgenic mice that express the P1-c subunit isoform under the promoter of the brown adipose tissue-specific protein UCP1. In the resulting UCP1p1 transgenic mice, total P1-c subunit mRNA levels were increased; mRNA levels of other F1Fo-ATPase subunits were unchanged. In isolated brown-fat mitochondria, protein levels of the total c-Fo subunit were increased. Remarkably, protein levels of ATP synthase subunits that are part of the F1-ATPase complex were also increased, as was the entire Complex V. Increased ATPase and ATP synthase activities demonstrated an increased functional activity of the F1Fo-ATPase. Thus, the levels of the c-Fo subunit P1-isoform are crucial for defining the final content of the ATP synthase in brown adipose tissue. The level of c-Fo subunit may be a determining factor for F1Fo-ATPase assembly in all higher eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / enzymology*
  • Animals
  • Base Sequence
  • Blotting, Western
  • DNA Primers
  • Founder Effect
  • Ion Channels / genetics
  • Ion Channels / physiology
  • Isoenzymes / metabolism*
  • Mice
  • Mice, Transgenic
  • Mitochondria / enzymology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / physiology
  • Proton-Translocating ATPases / metabolism*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uncoupling Protein 1


  • DNA Primers
  • Ion Channels
  • Isoenzymes
  • Mitochondrial Proteins
  • RNA, Messenger
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Proton-Translocating ATPases