Mitochondrial alterations in apoptosis

•The mitochondrial outer membrane permeabilization (MOMP) is the key step in the intrinsic pathway of apoptosis.•Bcl-2 family proteins are the main regulators of MOMP.•MOMP causes the release of proapoptotic factors into the cytosol, which activate caspases and induce apoptosis.•Mitochondrial loss of functions and morphological changes (fission and cristae remodeling) are concomitant or follow MOMP.

Besides their conventional role as energy suppliers for the cell, mitochondria in vertebrates are active regulators of apoptosis. They release apoptotic factors from the intermembrane space into the cytosol through a mechanism that involves the Bcl-2 protein family, mediating permeabilization of the outer mitochondrial membrane. Associated with this event, a number of additional changes affect mitochondria during apoptosis. They include loss of important mitochondrial functions, such as the ability to maintain calcium homeostasis and to generate ATP, as well as mitochondrial fragmentation and cristae remodeling. Moreover, the lipidic component of mitochondrial membranes undergoes important alterations in composition and distribution, which have turned out to be relevant regulatory events for the proteins involved in apoptotic mitochondrial damage.