Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1813, Issue 6, Pages 1239-1244Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2011.03.017
Keywords
MEK1/2; PGC-1 beta; Mitochondrial biogenesis
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Funding
- Chinese Academy of Sciences [KSCX2-YW-R-084]
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Growth factor activates mitogen-activated protein kinase kinases to promote cell growth. Mitochondrial biogenesis is an integral part of cell growth. How growth factor regulates mitochondrial biogenesis is not fully understood. In this study, we found that mitochondrial mass was specifically reduced upon serum starvation and induced upon re-feeding with serum. Using mitogen-activated protein kinase kinases inhibitor U0126, we found that the mRNA expression levels of ATP synthase, cytochrome-C, mitochondrial transcription factor A, and mitofusin 2 were reduced. Since the transcriptional levels of these genes are under the control of peroxisome proliferator-activated receptor gamma coactivator-1 alpha and -1 beta (PGC-1 alpha and PGC-1 beta), we examined and found that only the mRNA and protein levels of PGC-1 beta were suppressed. Importantly, over-expression of PGC-1 beta partially reversed the reduction of mitochondrial mass upon U0126 treatment. Thus, we conclude that mitogen-activated protein kinase kinases direct mitochondrial biogenesis through selectively inducing PGC-1 beta expression. (C) 2011 Elsevier B.V. All rights reserved.
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