Is mPTP the gatekeeper for necrosis, apoptosis, or both?
Permeabilization of the mitochondrial membranes is a crucial step in apoptosis and necrosis. This phenomenon allows the release of mitochondrial death factors, which trigger or facilitate different signaling cascades ultimately causing the execution of the cell. The mitochondrial permeability transition pore (mPTP) has long been known as one of the main regulators of mitochondria during cell death. mPTP opening can lead to matrix swelling, subsequent rupture of the outer membrane, and a nonspecific release of intermembrane space proteins into the cytosol. While mPTP was purportedly associated with early apoptosis, recent observations suggest that mitochondrial permeabilization mediated by mPTP is generally more closely linked to events of late apoptosis and necrosis. Mechanisms of mitochondrial membrane permeabilization during cell death, involving three different mitochondrial channels, have been postulated. These include the mPTP in the inner membrane, and the mitochondrial apoptosis-induced channel (MAC) and voltage-dependent anion-selective channel (VDAC) in the outer membrane. New developments on mPTP structure and function, and the involvement of mPTP, MAC, and VDAC in permeabilization of mitochondrial membranes during cell death are explored. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.
Kinnally
Kathleen W
KW
New York University College of Dentistry, Department Basic Sciences 345 East 24th Street, New York, NY 10010, USA.
Peixoto
Pablo M
PM
Ryu
Shin-Young
SY
Dejean
Laurent M
LM
D000818:Animals; D017209:Apoptosis; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D009336:Necrosis
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore