title: Mitogen-activated protein kinase kinases promote mitochondrial biogenesis in part through inducing peroxisome proliferator-activated receptor γ coactivator-1β expression.
abstract: 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 γ coactivator-1α and -1β (PGC-1α and PGC-1β), we examined and found that only the mRNA and protein levels of PGC-1β were suppressed. Importantly, over-expression of PGC-1β 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-1β expression.
authors: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 510530 China.
authors: Minghui
authors: M
authors: Gao
authors: Junjian
authors: J
authors: Wang
authors: Na
authors: N
authors: Lu
authors: Fang
authors: F
authors: Fang
authors: Jinsong
authors: J
authors: Liu
authors: Chi-Wai
authors: CW
authors: Wong
mesh_terms: D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020558:GTP Phosphohydrolases; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D002070:Butadienes; D002352:Carrier Proteins; D045304:Cytochromes c; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020558:GTP Phosphohydrolases; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D025261:Mitochondrial Proton-Translocating ATPases; D020929:Mitogen-Activated Protein Kinase Kinases; D009570:Nitriles; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C506526:ATP5F1B protein, human; C490917:ESRRG protein, human; C486497:PPARGC1A protein, human; C455622:PPARGC1B protein, human; C113580:U 0126; C422562:mitochondrial transcription factor A; C470018:MFN2 protein, human