HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-8581comv1 22/1/55    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kramarova, T. V. Articles by Cannon, B. PubMed PubMed Citation Articles by Kramarova, T. V. Articles by Cannon, B.

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

Tatiana V. Kramarova^*,1, Irina G. Shabalina^*, Ulf Andersson^*,2, Rolf Westerberg^*,2, Inger Carlberg, Josef Houstek, Jan Nedergaard^* and Barbara Cannon^*,3

^* The Wenner-Gren Institute and

Department of Biochemistry and Biophysics, The Arrhenius Laboratories, Stockholm University, Stockholm, Sweden; and

Department of Bioenergetics, Institute of Physiology and Centre for Applied Genomics, Prague, Czech Republic

³Correspondence: The Wenner-Gren Institute, The Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. E-mail: barbara.cannon{at}wgi.su.se

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-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 UCP1p1 transgenic mice, total P1-c subunit mRNA levels were increased; mRNA levels of other F₁F_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 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 F₁F_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 F₁F_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.

Key Words: biogenesis • assembly • UCP1 promoter • transgenic mice