Abstract
AbstractThe mitochondrial permeability transition (mPT) describes a Ca2+-dependent and cyclophilin D (CypD)-facilitated increase of inner mitochondrial membrane permeability that allows diffusion of molecules up to 1.5 kDa in size. It is mediated by a non-selective channel, the mitochondrial permeability transition pore (mPTP). Sustained mPTP opening causes mitochondrial swelling, which ruptures the outer mitochondrial membrane leading to subsequent apoptotic and necrotic cell death, and is implicated in a range of pathologies. However, transient mPTP opening at various sub-conductance states may contribute several physiological roles such as alterations in mitochondrial bioenergetics and rapid Ca2+ efflux. Since its discovery decades ago, intensive efforts have been made to identify the exact pore-forming structure of the mPT. Both the adenine nucleotide translocase (ANT) and, more recently, the mitochondrial F1FO (F)-ATP synthase dimers, monomers or c-subunit ring alone have been implicated. Here we share the insights of several key investigators with different perspectives who have pioneered mPT research. We critically assess proposed models for the molecular identity of the mPTP and the mechanisms underlying its opposing roles in the life and death of cells. We provide in-depth insights into current controversies, seeking to achieve a degree of consensus that will stimulate future innovative research into the nature and role of the mPTP.
Funder
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
AIRIcerca
Fondation Leducq
Japan Agency for Medical Research and Development
MEXT | JST | Center of Innovation Program
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke
U.S. Department of Health & Human Services | NIH | National Institute on Aging
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology
Cited by
20 articles.
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