Abstract

An event now recognized to be important in ontogenesis of both muscle cells and mitochondria (mit.) is the mit. permeability transition (MPT). MPT represents an abrupt increase of permeability of the mit. inner membrane following Ca2+ uptake. Exercise is associated with changes in intracellular milieu that may promote MPT pore assembly (e.g. increase in Ca2+ and Pi, oxidative stress). PURPOSE To investigate the effect of single bout of prolonged exercise on the capacity of muscle mit. to sequester Ca2+ and resist MPT. METHODS 7 subjects performed 75 min of cycling at 70% of VO2peak. Mit. were isolated from biopsies taken from the lateral aspect of the m. quadriceps femoris before, immediately after and 2 h after the exercise. Mit. swelling was monitored as changes in A540. Ca2+ pulses (2 μmol of Ca2+/U citrate synthase (CS)) were added every 3 min to the mit. energized with pyruvate+malate until rapid swelling of mit. indicating MPT opening was induced. RESULTS Mit. from samples taken prior to exercise buffered 8.6±0.8 μmol of Ca2+/U CS before they had been saturated and MPT pore was opened. Mit. from samples taken immediately after exercise had a significantly better capacity to sequester repeated Ca2+ loads (13.2±1.2 μmol Ca2+/U CS, P <0.01 vs pre-exercise value). After 2 h recovery the amount of Ca2+ required to elicit progressive swelling of isolated mit. (10.0±0.8 μmol Ca2+/U CS) was not significantly different from that prior to exercise. CONCLUSION Prolonged exercise induces a reversible increase in mit. capacity to accumulate Ca2+ and resist MPT. This effect of exercise resembles protective effect of calcium- or ischemia preconditioning that is known to inhibit MPT and preserve mit. function. MPT opening is a prerequisite for degradation of mit. by the process of autophagy. Improved mit. MPT-resistance induced by prolonged exercise may decrease the rate of degradation of muscle mit. and contribute, along with increased rate of mit. biogenesis, to expansion of muscle mit. mass induced by endurance training.

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