Mitochondrial Permeability Transition Pore

The mitochondrial permeability transition pore (MPTP) is a Ca²⁺-dependent, nonselective pore located on the inner mitochondrial membrane. It opens in response to elevated matrix Ca²⁺ concentrations, increasing the permeability of the mitochondrial membrane to molecules less than 1.5 kDa in weight, and resulting in cell death.

Under normal physiological conditions, MPTP is closed; if matrix [Ca²⁺] increases, the pore opens, causing /a mitochondrial permeability transition (MPT) and resulting in mitochondrial swelling. Other conditions, such as oxidative stress, mitochondrial depolarization and depletion of adenine nucleotides, also influence MPT by helping sensitize the pore to calcium concentrations. MPTP opening can trigger different types of cell death. Transient opening results in the release of cytochrome c, which activates the caspase cascade and triggers apoptosis. Sustained pore opening results in the uncoupling of oxidative phosphorylation; this limits ATP synthesis and leads to necrotic cell death.

The structure of MPTP is yet to be elucidated, but components such as cyclophilin D (Cyp-D), the adenine nucleotide translocator (ANT) and voltage-dependent anion channels (VDAC) have been linked to either the formation or regulation of the pore. Consequently, agents that selectively inhibit these components have often been used in the study of MPT. Targeting the mitochondrial permeability transition pore may provide a viable therapeutic avenue for a variety of conditions. For example, in reperfusion injury, the heart experiences conditions similar to those that induce the opening of MPTP (such as oxidative stress); therefore the potential cardioprotective capacity of MPTP inhibition has been the subject of much research. Additionally, regulation of mitochondrial membrane permeability may confer neuroprotection and help illuminate the role of MPTP in neurodegeneration.

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Programmed Cell Death Poster

There are two currently recognized forms of programmed cell death: apoptosis and necroptosis. This poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate.

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Mitochondrial Permeability Transition Pore Gene Data