Mitochondrial permeability transition and cell death: the role of cyclophilin D

Mitochondria serve as a powerhouse which provides near 90% of ATP necessary for cell life. However, recent studies provide strong evidence that mitochondria also play a central role in cell death. Irreversible mitochondrial permeability transition (mPT) at high conductance in response to oxidative...

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Main Authors: Sabzali eJavadov, Andrey eKuznetsov
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-04-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2013.00076/full
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author Sabzali eJavadov
Andrey eKuznetsov
author_facet Sabzali eJavadov
Andrey eKuznetsov
author_sort Sabzali eJavadov
collection DOAJ
description Mitochondria serve as a powerhouse which provides near 90% of ATP necessary for cell life. However, recent studies provide strong evidence that mitochondria also play a central role in cell death. Irreversible mitochondrial permeability transition (mPT) at high conductance in response to oxidative or other cellular stresses is accompanied by formation of pathological and non-specific mPT pores (mPTP) in the inner membrane of mitochondria. Mitochondrial PTP can serve as a target to prevent cell death under pathological conditions such as cardiac and brain ischemia/reperfusion injury and diabetes. On the other hand, mPTP can be used as an executioner to specifically induce cell death thus blocking tumorigenesis in cancer diseases. Despite many studies, the molecular identity of the mPTP remains unclear. At present, cyclophilin D (CyP-D) represents the only mPTP protein which plays an essential role in pore formation. This review will discuss direct and indirect mechanisms underlying CyP-D interaction with a target protein of the mPTP complex. Understanding of the mechanisms of mPTP formation will be helpful to further develop new pharmacological agents targeting mitochondria-mediated cell death.
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spelling doaj.art-9744deccc40442d1a51a62a4e349340d2022-12-21T20:34:38ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2013-04-01410.3389/fphys.2013.0007645409Mitochondrial permeability transition and cell death: the role of cyclophilin DSabzali eJavadov0Andrey eKuznetsov1University of Puerto Rico School of MedicineInnsbruck Medical UniversityMitochondria serve as a powerhouse which provides near 90% of ATP necessary for cell life. However, recent studies provide strong evidence that mitochondria also play a central role in cell death. Irreversible mitochondrial permeability transition (mPT) at high conductance in response to oxidative or other cellular stresses is accompanied by formation of pathological and non-specific mPT pores (mPTP) in the inner membrane of mitochondria. Mitochondrial PTP can serve as a target to prevent cell death under pathological conditions such as cardiac and brain ischemia/reperfusion injury and diabetes. On the other hand, mPTP can be used as an executioner to specifically induce cell death thus blocking tumorigenesis in cancer diseases. Despite many studies, the molecular identity of the mPTP remains unclear. At present, cyclophilin D (CyP-D) represents the only mPTP protein which plays an essential role in pore formation. This review will discuss direct and indirect mechanisms underlying CyP-D interaction with a target protein of the mPTP complex. Understanding of the mechanisms of mPTP formation will be helpful to further develop new pharmacological agents targeting mitochondria-mediated cell death.http://journal.frontiersin.org/Journal/10.3389/fphys.2013.00076/fullCell DeathMitochondriaOxidative Stresspermeability transition poreCyclophilin D
spellingShingle Sabzali eJavadov
Andrey eKuznetsov
Mitochondrial permeability transition and cell death: the role of cyclophilin D
Frontiers in Physiology
Cell Death
Mitochondria
Oxidative Stress
permeability transition pore
Cyclophilin D
title Mitochondrial permeability transition and cell death: the role of cyclophilin D
title_full Mitochondrial permeability transition and cell death: the role of cyclophilin D
title_fullStr Mitochondrial permeability transition and cell death: the role of cyclophilin D
title_full_unstemmed Mitochondrial permeability transition and cell death: the role of cyclophilin D
title_short Mitochondrial permeability transition and cell death: the role of cyclophilin D
title_sort mitochondrial permeability transition and cell death the role of cyclophilin d
topic Cell Death
Mitochondria
Oxidative Stress
permeability transition pore
Cyclophilin D
url http://journal.frontiersin.org/Journal/10.3389/fphys.2013.00076/full
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