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Mitochondrial ATP synthase levels in brown adipose tissue are governed by the c‐Fo subunit P1 isoform
Author(s) -
Kramarova Tatiana V.,
Shabalina Irina G.,
Andersson Ulf,
Westerberg Rolf,
Carlberg Inger,
Houstek Josef,
Nedergaard Jan,
Can Barbara
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8581com
Subject(s) - atp synthase , protein subunit , brown adipose tissue , gene isoform , atpase , v atpase , mitochondrion , thermogenin , mitochondrial biogenesis , biology , atp synthase gamma subunit , biochemistry , f atpase , respiratory chain , chemistry , adipose tissue , microbiology and biotechnology , enzyme , atp hydrolysis , gene , thylakoid , chloroplast
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 syn‐thase, 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‐F o 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 UCPlpl transgenic mice, total P1‐c subunit mRNA levels were increased;mRNA levels of other F 1 F o ‐ATPase subunits were unchanged. In isolated brown‐fat mitochondria, protein levels of the total c‐F o subunit were increased. Remarkably, protein levels of ATP synthase subunits that are part of the F 1 ‐ATPase complex were also increased, as was the entire Complex V. Increased ATPase and ATP synthase activities demonstrated an increased functional activity of the F 1 F o ‐ATPase. Thus, the levels of the c‐F o subunit P1‐isoform are crucial for defining the final content of the ATP synthase in brown adipose tissue. The level of c‐F o subunit may be a determining factor for F 1 F o ‐ATPase assembly in all higher eukaryotes.— Kramarova T. V., Shabalina, I. G., Andersson, U., Westerberg, R., Carlberg, I., Houstek, J., Nedergaard, J., Cannon B. Mitochondrial ATP synthase levels in brown adipose tissue are governed by the c‐Fo subunit P1 isoform. FASEB J. 22, 55–63 (2008)