Halling 2019 Am J Physiol Endocrinol Metab
|Halling JF, Jessen H, Nøhr-Meldgaard J, Thiellesen Buch B, Masselkhi Christensen N, Gudiksen A, Ringholm S, Neufer PD, Prats C, Pilegaard H (2019) PGC-1α regulates mitochondrial properties beyond biogenesis with aging and exercise training. Am J Physiol Endocrinol Metab 317:E513-E525.|
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 co-activator PGC-1α. Recently, mitochondrial ADP sensitivity has been linked to 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 controls. Aged mice displayed lower running endurance and mitochondrial respiratory capacity than young. 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-1a, while exercise training rescued the age-related mitochondrial network fragmentation and 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 ANT1. 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.
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Exercise physiology;nutrition;life style Pathology: Aging;senescence
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k, O2k-Fluorometer