Mitochondrial apoptosis-induced channel

The mitochondrial apoptosis-induced channel (or MAC), is an early marker of the onset of apoptosis.^[2][3] This ion channel is formed on the outer mitochondrial membrane in response to certain apoptotic stimuli.^[4] MAC activity is detected by patch clamping mitochondria from apoptotic cells at the time of cytochrome c release.^[5]

Members of the Bcl-2 protein family regulate apoptosis by controlling the formation of MAC: the pro-apoptotic members Bax and/or Bak form MAC,^[1][5] whereas the anti-apoptotic members like Bcl-2 or Bcl-xL prevent MAC formation. Once formed, MAC mediates the release of cytochrome c to the cytosol, triggering the commitment step of the mitochondrial apoptotic cascade. Depletion of MAC activity is accomplished pharmacologically by specific compounds, namely Bax channel inhibitors^[6] and MAC inhibitors.^[7] Either by knocking down MAC's main components or by its pharmacological inhibition, the end result is prevention of cytochrome c release and apoptosis.