| First Author | Halling JF | Year | 2019 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 317 |
| Issue | 3 | Pages | E513-E525 |
| PubMed ID | 31265325 | Mgi Jnum | J:283683 |
| Mgi Id | MGI:6376773 | Doi | 10.1152/ajpendo.00059.2019 |
| Citation | Halling JF, et al. (2019) PGC-1alpha regulates mitochondrial properties beyond biogenesis with aging and exercise training. Am J Physiol Endocrinol Metab 317(3):E513-E525 |
| abstractText | 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 gamma coactivator-1alpha (PGC-1alpha). 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-1alpha-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-1alpha, whereas exercise training rescued the age-related mitochondrial network fragmentation and the impaired submaximal ADP-stimulated respiration in a PGC-1alpha-dependent manner. Furthermore, lack of PGC-1alpha 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-1alpha regulates submaximal ADP-stimulated respiration, ROS emission, and mitochondrial network structure in mouse skeletal muscle during aging and exercise training. |
