Mitochondrial ATP synthase levels in brown adipose tissue are governed by the c-Fo subunit P1 isoform.
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.
Kramarova
Tatiana V
TV
The Wenner-Gren Institute, The Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden.
Shabalina
Irina G
IG
Andersson
Ulf
U
Westerberg
Rolf
R
Carlberg
Inger
I
Houstek
Josef
J
Nedergaard
Jan
J
Cannon
Barbara
B
D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D018703:Founder Effect; D007473:Ion Channels / Q000235:genetics / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071256:Uncoupling Protein 1
D017931:DNA Primers; D007473:Ion Channels; D007527:Isoenzymes; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D006180:Proton-Translocating ATPases