Mitochondrial Biogenesis in Neurodegeneration

Mitochondria play a key role in energy production, calcium homeostasis, cell survival, and death. Adverse stimulations including neurodegenerative diseases may result in mitochondria' dynamic imbalance, free radical production, calcium accumulation, intrinsic cell death pathway activation and eventually cell death. Therefore, preserving or promoting mitochondrial function is a potential therapeutic target for the treatment of neurodegenerative disorders. Mitochondrial biogenesis is a process by which new mitochondria are produced from existing mitochondria. This biogenesis process is regulated by Peroxisonne proliferator-activated receptor-gamma (PPAR-gamma) coactivator-1alpha (PGC-1 alpha). Once being activated by either phosphorylation or de-acetylation, PGC-1 alpha activates nuclear respiratory factor 1 and 2 (NRF1 and NRF2), and subsequently mitochondria' transcription factor A (Tfam). The activation of this PGC-1 alpha - NRF -Tfam pathway leads to synthesis of mitochondrial DNA and proteins and generation of new mitochondria. (C) 2017 Wiley Periodicals, Inc.