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 mitochondrial membrane permeability.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
1101 Cyclosporin A
Inhibits MPTP opening
2906 TRO 19622
Binds VDAC; thought to inhibit MPTP opening

Other

Cat No Product Name / Activity
4600 Auranofin
Thioredoxin reductase inhibitor; induces MPT

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.

Literature for Mitochondrial Permeability Transition Pore

Cardiovascular

Cardiovascular Research Product Guide

A collection of over 250 products for cardiovascular research, the guide includes research tools for the study of:

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Programmed Cell Death

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Mitochondrial Permeability Transition Pore Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Voltage-dependent anion channel 1 Human VDAC1 NR_036624 P21796
Mouse Vdac1 NM_011694 Q60932
Rat Vdac1 NM_031353 Q9Z2L0
Peptidylprolyl isomerase F (Cyclophilin-D) Human PPIF NM_005729 P30405
Mouse Ppif NM_134084 Q99KR7
Rat Ppif NM_172243 P29117