Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1α itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets.
Review Article| June 14 2010
Regulation of mitochondrial biogenesis
François R. Jornayvaz;
Gerald I. Shulman
Gerald I. Shulman 1
*Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536, U.S.A.
†Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06536, U.S.A.
‡Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, U.S.A.
1To whom correspondence should be addressed (firstname.lastname@example.org).
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Essays Biochem (2010) 47: 69–84.
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Guy C. Brown, Michael P. Murphy, François R. Jornayvaz, Gerald I. Shulman; Regulation of mitochondrial biogenesis. Essays Biochem 14 June 2010; 47 69–84. doi: https://doi.org/10.1042/bse0470069
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