PGC-1α: a master gene that is hard to master.
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that favorably affects mitochondrial function. This concept is supported by an increasing amount of data including studies in PGC-1α gene-deleted mice, suggesting that PGC-1α is a rescue factor capable of boosting cell metabolism and promoting cell survival. However, this view has now been called into question by a recent study showing that adeno-associated virus-mediated PGC-1α overexpression causes overt cell degeneration in dopaminergic neurons. How is this to be understood, and can these seemingly conflicting findings tell us something about the role of PGC-1α in cell stress and in control of neuronal homeostasis?
Institute of Biomedicine, Biochemistry and Developmental Biology, University of Helsinki, Finland. dan.lindholm@helsinki.fi
Dan
D
Lindholm
Ove
O
Eriksson
Johanna
J
Mäkelä
Natale
N
Belluardo
Laura
L
Korhonen
D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology; D008959:Models, Neurological; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors