FIGURE 4.

Exercise-induced signaling pathways regulate mitochondrial ROS level. (A) In the aspect of the excitation-transcription events, the ATP deficit during exercise induces AMPK activation, which can both directly phosphorylate and increase the expression of PGC-1α, the pivotal player in countering ROS-related damages. P38 MAPK and certain CAMKs have also been demonstrated to be activated by exercise and induce PGC-1α expression. SIRT1 activation promotes deacetylation of PGC-1α, enhancing its transcriptional activities. On the other hand, SIRT1 represses the expression of uncoupling protein (UCP2, UCP3). UCP induced mild depolarization of IMM accelerates electron flux along the respiratory chain, decreases the level of ubisemiquinone (UQ) and hence reduces superoxide production. Thus, the impact of SIRT1 activation on ROS level is mixed. In contrast, another SIRT family member SIRT3 promotes UCP expression by inhibiting JNK activation. It also promotes superoxide removal through deacetylating SOD2. (B) The rapid mitochondrial Ca²⁺ flux induced by motor neuron input may decrease ROS production through increasing the turnover rate of the respiratory chain or suppressing mPTP opening.