PGC-1α: a master gene that is hard to master
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- Lindholm, D., Eriksson, O., Mäkelä, J. et al. Cell. Mol. Life Sci. (2012) 69: 2465. doi:10.1007/s00018-012-1043-0
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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?