Mitochondria play an important role in energy metabolism of the cell. The electron transport chain linked to oxidative phosphorylation provides ATP necessary for cell metabolism. Studies over the past 30 years provide strong evidence that, in addition to their role in cell life, mitochondria are the main organelles which initiate cell death through apoptosis, necrosis, and autophagy. One of the key events that cause mitochondria-mediated cell death is the mitochondrial permeability transition (PT) that associates with formation of non-selective pathological PT pores (PTPs) in the inner membrane of mitochondria (IMM). Oxidative stress, Ca2+ accumulation, and ATP depletion are the main factors inducing mitochondrial PT which is accompanied by loss of membrane potential (Δψm ) and proton gradient (ΔpH) across the IMM. Loss of electrochemical potential diminishes oxidative phosphorylation and ATP synthesis. Mitochondrial PTP formation can occur at low (or transient) conductance, and at high (or long-lasting) conductance, although the existence of a low-conductance mode (reversible opening of PTP) is still controversial. In a high-conductance mode, which has been accepted as an irreversible step, solutes, water and ions with the molecular mass up to ~1.5 kD enter through the PTPs thus enhancing colloid-osmotic pressure in the matrix [1,2] (Figure 1). Surface area of the IMM exceeds that of the outer mitochondrial membrane (OMM), and extensive matrix swelling induces unfolding of cristae causing rupture of the OMM. Damage to the OMM leads to cell death through apoptosis and/or necrosis depending on the ATP level in the cell. When ATP synthesis is partially maintained by undamaged mitochondria, release of pro-apoptotic proteins will initiate cell death through caspase-dependent (e.g. cytochrome c, Smac/DIABLO) and/ or caspase-independent (e.g. AIF, EndoG) pathways. However, in the absence of ATP, cell death will preferably occur through necrosis even though mitochondrial pro-apoptotic proteins are present in the cytoplasm [3-5].
Javadov S (2012) Mitochondrial Permeability Transition: Known Phenomenon with Unknown Molecular Identity. Anat Physiol 2:e117.