Voltage-dependent Anion Channels Control the Release of the Superoxide Anion from Mitochondria to Cytosol

Several reactions in biological systems contribute to maintain the steady-state concentrations of superoxide anion (O 2⨪) and hydrogen peroxide (H2O2). The electron transfer chain of mitochondria is a well documented source of H2O2; however, the release of O 2⨪ from mitochondria into cytosol has not been unequivocally established. This study was aimed at validating mitochondria as sources of cytosolic O 2⨪, elucidating the mechanisms underlying the release of O 2⨪ from mitochondria into cytosol, and assessing the role of outer membrane voltage-dependent anion channels (VDACs) in this process. Isolated rat heart mitochondria supplemented with complex I or II substrates generate an EPR signal ascribed to O 2⨪.…