Regulation of PPAR𝛾 Coactivator-1𝛼 Function and Expression in Muscle: Effect of Exercise

Figure 1

PGC-1$\alpha$ induces expression of nuclear and mitochondrial genes required for organelle synthesis. Expression of PPAR$\gamma$ coactivator-1α is regulated by a number of transcription factors (e.g., USF-1, CREB) which associate with its promoter region to augment transcription. External stimuli, such as exercise, provoke the formation of reactive oxygen species (ROS) and activate AMPK. These signalling molecules induce PGC-1α transcription (1), and increase coactivator mRNA expression. Upon formation, the nascent transcript is transported to the cytoplasm. Once translated into protein, PGC-1$\alpha$ is sequestered to the nucleus (2), interacting with transcription factors to promote the transcription of nuclear genes encoding mitochondrial proteins (NUGEMPs). Specifically, PGC-1$\alpha$ is known to associate with nuclear respiratory factors 1 and 2 (NRF-1, NRF-2), guiding the transcription of mitochondrially-destined proteins. NUGEMP mRNA is exported to the cytoplasm and is subject to translation (3). The translated precursor proteins are imported into the mitochondria (4) via the protein import machinery (PIM). Many of these form multisubunit complexes that become part of the electron transport chain (ETC). One particular nuclear-derived protein is mitochondrial transcription factor A (Tfam). Once imported into the mitochondria, it associates with mitochondrial DNA (mtDNA) (5), directing the production of mtDNA-encoded proteins. These products are then integrated into the ETC (6). Thus, PGC-1α is an important protein which initiates a cascade of events leading to mitochondrial biogenesis.