PGC-1α regulates mitochondrial properties beyond biogenesis with aging and exercise training

PGC-1α regulates mitochondrial properties beyond biogenesis with aging and exercise training Impaired mitochondrial function has been implicated in the pathogenesis of age-associated metabolic diseases through regulation of cellular redox balance. Exercise training is known to promote mitochondrial biogenesis in part through induction of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Recently, mitochondrial ADP sensitivity has been linked to reactive oxygen species (ROS) emission with potential impact on age-associated physiological outcomes, but the underlying molecular mechanisms remain unclear. Therefore, the present study investigated the effects of aging and exercise training on mitochondrial properties beyond biogenesis, including respiratory capacity, ADP sensitivity, ROS emission, and mitochondrial network structure, in myofibers from inducible muscle-specific PGC-1α-knockout mice and control mice. Aged mice displayed lower running endurance and mitochondrial respiratory capacity than young mice. This was associated with intermyofibrillar mitochondrial network fragmentation, diminished submaximal ADP-stimulated respiration, increased mitochondrial ROS emission, and oxidative stress. Exercise training reversed the decline in maximal respiratory capacity independent of PGC-1α, whereas exercise training rescued the age-related mitochondrial network fragmentation and the impaired submaximal ADP-stimulated respiration in a PGC-1α-dependent manner. Furthermore, lack of PGC-1α was associated with altered phosphorylation and carbonylation of the inner mitochondrial membrane ADP/ATP exchanger adenine nucleotide translocase 1. In conclusion, the present study provides evidence that PGC-1α regulates submaximal ADP-stimulated respiration, ROS emission, and mitochondrial network structure in mouse skeletal muscle during aging and exercise training. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Endocrinology and Metabolism The American Physiological Society

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ISSN
0193-1849
eISSN
1522-1555
DOI
10.1152/ajpendo.00059.2019
Publisher site
See Article on Publisher Site

Abstract

Impaired mitochondrial function has been implicated in the pathogenesis of age-associated metabolic diseases through regulation of cellular redox balance. Exercise training is known to promote mitochondrial biogenesis in part through induction of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Recently, mitochondrial ADP sensitivity has been linked to reactive oxygen species (ROS) emission with potential impact on age-associated physiological outcomes, but the underlying molecular mechanisms remain unclear. Therefore, the present study investigated the effects of aging and exercise training on mitochondrial properties beyond biogenesis, including respiratory capacity, ADP sensitivity, ROS emission, and mitochondrial network structure, in myofibers from inducible muscle-specific PGC-1α-knockout mice and control mice. Aged mice displayed lower running endurance and mitochondrial respiratory capacity than young mice. This was associated with intermyofibrillar mitochondrial network fragmentation, diminished submaximal ADP-stimulated respiration, increased mitochondrial ROS emission, and oxidative stress. Exercise training reversed the decline in maximal respiratory capacity independent of PGC-1α, whereas exercise training rescued the age-related mitochondrial network fragmentation and the impaired submaximal ADP-stimulated respiration in a PGC-1α-dependent manner. Furthermore, lack of PGC-1α was associated with altered phosphorylation and carbonylation of the inner mitochondrial membrane ADP/ATP exchanger adenine nucleotide translocase 1. In conclusion, the present study provides evidence that PGC-1α regulates submaximal ADP-stimulated respiration, ROS emission, and mitochondrial network structure in mouse skeletal muscle during aging and exercise training.

Journal

AJP - Endocrinology and MetabolismThe American Physiological Society

Published: Sep 1, 2019

References

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