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Transcriptional integration of mitochondrial biogenesis

2012; Elsevier BV; Volume: 23; Issue: 9 Linguagem: Inglês

10.1016/j.tem.2012.06.006

1879-3061

Richard C. Scarpulla, Rick B. Vega, Daniel P. Kelly,

Mitochondrial Function and Pathology

Gene regulatory factors encoded by the nuclear genome are essential for mitochondrial biogenesis and function. Some of these factors act exclusively within the mitochondria to regulate the control of mitochondrial transcription, translation, and other functions. Others govern the expression of nuclear genes required for mitochondrial metabolism and organelle biogenesis. The peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family of transcriptional coactivators play a major role in transducing and integrating physiological signals governing metabolism, differentiation, and cell growth to the transcriptional machinery controlling mitochondrial functional capacity. Thus, the PGC-1 coactivators serve as a central component of the transcriptional regulatory circuitry that coordinately controls the energy-generating functions of mitochondria in accordance with the metabolic demands imposed by changing physiological conditions, senescence, and disease. Gene regulatory factors encoded by the nuclear genome are essential for mitochondrial biogenesis and function. Some of these factors act exclusively within the mitochondria to regulate the control of mitochondrial transcription, translation, and other functions. Others govern the expression of nuclear genes required for mitochondrial metabolism and organelle biogenesis. The peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family of transcriptional coactivators play a major role in transducing and integrating physiological signals governing metabolism, differentiation, and cell growth to the transcriptional machinery controlling mitochondrial functional capacity. Thus, the PGC-1 coactivators serve as a central component of the transcriptional regulatory circuitry that coordinately controls the energy-generating functions of mitochondria in accordance with the metabolic demands imposed by changing physiological conditions, senescence, and disease. an energy-sensing kinase that directly phosphorylates and enhances the activity of PGC-1. a mitochondrial methyltransferase that dimethylates 12S rRNA and controls the stability or assembly of the mitochondrial ribosome. a family of orphan nuclear receptors that are involved in the regulation of virtually all aspects of mitochondrial function and biogenesis. an acetyltransferase that acetylates and inhibits activity of PGC-1α and β. a transcription factor that functions as a homodimer and activates the expression of key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. a multisubunit transcription factor that is involved in cytochrome oxidase expression and the nuclear control of mitochondrial function. a family of ligand-activated nuclear receptors that regulate various aspects of lipid and fatty acid metabolism as well as cellular differentiation. a third member of the PGC-1 family that also binds to transcription factors important for mitochondrial biogenesis and function. transcriptional coactivators that bind to several target transcription factors involved in cellular energy metabolism and mitochondrial function including PPARs, ERRs and NRF-1 and -2. a mitochondrial DNA-directed RNA polymerase. also termed mtTFA, is a mitochondrial transcription factor that is a key activator of mitochondrial transcription and participates in mitochondrial genome replication. a ubiquitously-expressed transcription factor that directs histone deacetylases and histone acetyltransferases to a promoter to activate or repress gene expression.