Key components of the mitochondrial permeability transition pore (MPTP) contributing to partial or complete loss of ΔψM. (A) Normal mitochondrial components of the outer mitochondrial membrane (OMM; voltage-dependent anion transporter, VDAC), inner mitochondrial membrane (IMM; adenine nucleotide transporter, ANT) and mitochondrial matrix (cyclophilin-D, CyP-D) undergo conformational change following moderate or severe stress, resulting in transient or (B) sustained formation of the MPTP, the latter ending in necrosis. Ca2+ overload, FAs and reactive oxygen species (ROS) contribute to induction of the MPTP, which allows passage of all particles up to 1.5 kDa, contributing to mitochondrial swelling and rupture.