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- W2000301075 abstract "Mitochondria are critical for cellular bioenergetics, and they mediate apoptosis within cells. We used whole body peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) knockout (KO) animals to investigate its role on organelle function, apoptotic signaling, and cytochrome- c oxidase activity, an indicator of mitochondrial content, in muscle and other tissues (brain, liver, and pancreas). Lack of PGC-1α reduced mitochondrial content in all muscles (17–44%; P < 0.05) but had no effect in brain, liver, and pancreas. However, the tissue expression of proteins involved in mitochondrial DNA maintenance [transcription factor A (Tfam)], import (Tim23), and remodeling [mitofusin 2 (Mfn2) and dynamin-related protein 1 (Drp1)] did not parallel the decrease in mitochondrial content in PGC-1α KO animals. These proteins remained unchanged or were upregulated ( P < 0.05) in the highly oxidative heart, indicating a change in mitochondrial composition. A change in muscle organelle composition was also evident from the alterations in subsarcolemmal and intermyofibrillar mitochondrial respiration, which was impaired in the absence of PGC-1α. However, endurance-trained KO animals did not exhibit reduced mitochondrial respiration. Mitochondrial reactive oxygen species (ROS) production was not affected by the lack of PGC-1α, but subsarcolemmal mitochondria from PGC-1α KO animals released a greater amount of cytochrome c than in WT animals following exogenous ROS treatment. Our results indicate that the lack of PGC-1α results in 1) a muscle type-specific suppression of mitochondrial content that depends on basal oxidative capacity, 2) an alteration in mitochondrial composition, 3) impaired mitochondrial respiratory function that can be improved by training, and 4) a greater basal protein release from subsarcolemmal mitochondria, indicating an enhanced mitochondrial apoptotic susceptibility." @default.
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- W2000301075 date "2009-07-01" @default.
- W2000301075 modified "2023-10-11" @default.
- W2000301075 title "The role of PGC-1α on mitochondrial function and apoptotic susceptibility in muscle" @default.
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- W2000301075 doi "https://doi.org/10.1152/ajpcell.00070.2009" @default.
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