MEDLINE Journals

    Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells.

    Authors
    Wu Z, Huang X, Feng Y, et al. 
    Source
    Proc Natl Acad Sci U S A 2006 Sep 26; 103(39):14379-84
    Abstract

    PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha) is a master regulator of mitochondrial biogenesis and plays an important role in several other aspects of energy metabolism. To identify upstream regulators of PGC-1alpha gene transcription, 10,000 human full-length cDNAs were screened for induction of the PGC-1alpha promoter. A number of activators of PGC-1alpha transcription were found; the most potent activator was the transducer of regulated CREB (cAMP response element-binding protein) binding protein (TORC) 1, a coactivator of CREB. The other two members of the TORC family, TORC2 and TORC3, also strongly activated PGC-1alpha transcription. TORCs dramatically induced PGC-1alpha gene transcription through CREB. Forced expression of TORCs in primary muscle cells induced the endogenous mRNA of PGC-1alpha and its downstream target genes in the mitochondrial respiratory chain and TCA cycle. Importantly, these changes in gene expression resulted in increased mitochondrial oxidative capacity measured by cellular respiration and fatty acid oxidation. Finally, we demonstrated that the action of TORCs in promoting mitochondrial gene expression and function requires PGC-1alpha. Previous studies had indicated that TORCs function as a calcium- and cAMP-sensitive coincidence detector and mediate individual and synergistic effects of these two pathways. Our results, together with previous findings, strongly suggest that TORCs play a key role in linking these external signals to the transcriptional program of adaptive mitochondrial biogenesis by activating PGC-1alpha gene transcription.

    Mesh
    Adenoviridae
    Animals
    Cytochromes c
    Gene Expression Profiling
    Gene Expression Regulation
    HeLa Cells
    Humans
    Mice
    Mitochondria
    Muscle Cells
    Oxidation-Reduction
    Phosphoproteins
    Promoter Regions, Genetic
    RNA, Messenger
    Trans-Activators
    Transcription Factors
    Transcription, Genetic
    Language

    eng

    Pub Type(s)
    Journal Article
    PubMed ID

    16980408

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