Mitochondrial Membrane Permeabilization in Apoptosis

Synonym

MMP

Definition

During apoptosis, many signals can converge to the mitochondrion to trigger the so-called mitochondrial membrane permeabilization (MMP), a rate-limiting step in the execution of the death process. These signals are mainly endogenous proteins, which translocate from an intracellular compartment (e.g., nucleus, cytosol, lysosomes, etc.) to the mitochondrial outer membrane (OM). Accumulation of modified lipids (e.g., oxidized cardiolipin, ceramide, etc.) and ions (e.g., Ca²⁺) by the mitochondrion can also influence MMP. Moreover, the intracellular milieu, such as pH, reactive oxygen species (ROS), and ATP levels, can contribute to define a permissive environment for MMP execution. Once initiated, MMP leads to the release of intermembrane space factors into the cytosol, caspase-dependent proteins, such as cytochrome c, Smac/DIABLO, and pro-caspases, and caspase-independent proteins such as apoptosis-inducing factor, AIF, and EndoG. The major consequence of these...