Mitochondria | Laboratory of Physiological Hygiene and Exercise Science

Mitochondrial biogenesis

Mitochondrial biogenesis is regulated primarily by PGC-1α, a master cofactor required for synthesis and transport of most mitochondrial proteins, mitochondrial DNA proliferation, and antioxidant enzyme expression. Overexpresion of PGC-1α leads to transformation to more oxidative muscle fibers, higher oxidative capacity, greater fat utilization, fiber hypertrophy and greater resistance to oxidative stress and inflammation. Our lab has demonstrated that increased PGC-1α via DNA transfection can ameliorate muscle atrophy caused by immobilization and this is accomplished by increased mitochondrial biogenesis and reduced mitophagy.

Mitophagy

Mitophagy is a process during which non-functional and "old" mitochondria are targeted for degradation through a pathway called mitophagy-lysosomal system. Many enzymes are involved in the identification, labeling, ubiquitation and degradation of damaged mitochondria. Dysregulation is implicated in numerous cell functions and pathogenic conditions. We have demonstrated that muscle inactivity can enhance mitophagy, associated with oxidative stress and inflammation, whereas PGC-1α transfection can inhibit mitophagy in muscle disuse atrophy.

Mitochondrial dynamics

Mitochondrial dynamics defines morphological and ultrastructural changes in mitochondria regulated by fusion and fission. Thus, the organelle used to be considered “peanut shell” is actually a dynamic reticular network constantly changing it shape. We have studied the expression of several key proteins that regulate fusion and fission, such as Mfn1/2, Fis 1, Opa-1, and DRP. It is obvious that muscle activity has profound influence on these gene expressions which ultimately determine mitochondrial turnover and function.