Role and regulation of mitochondrial permeability transition in cell death
type: CreativeWork
description: The role of the Mitochondrial Permeability Transition (MPT) in apoptosis and necrosis is controversial. Here we show that the MPT regulates the release of cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling the cristae junction (CJ). CEM cells were treated with the ER-stressor thapsigargin (THG) which led to cyclophilin-D-dependent mitochondrial release of the profusion GTPase Optic Atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and cytochrome c release after THG treatment, but did not prevent the MPT showing that Bax was essential for cytochrome c release by MPT. In isolated mitochondria, MPT led to OPA1 and cytochrome c release independently of VDAC and the outer membrane indicating that the MPT is an inner membrane phenomenon. Lastly, the MPT was regulated by the electron transport chain since THG-induced cell death was inhibited in cells lacking mtDNA.
abstract: The role of the Mitochondrial Permeability Transition (MPT) in apoptosis and necrosis is controversial. Here we show that the MPT regulates the release of cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling the cristae junction (CJ). CEM cells were treated with the ER-stressor thapsigargin (THG) which led to cyclophilin-D-dependent mitochondrial release of the profusion GTPase Optic Atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and cytochrome c release after THG treatment, but did not prevent the MPT showing that Bax was essential for cytochrome c release by MPT. In isolated mitochondria, MPT led to OPA1 and cytochrome c release independently of VDAC and the outer membrane indicating that the MPT is an inner membrane phenomenon. Lastly, the MPT was regulated by the electron transport chain since THG-induced cell death was inhibited in cells lacking mtDNA.
author: ZHANG DAWEI
keywords: mitochondrial permeability transition, cytochrome c, OPA1, cyclophilin-D, cristae remodeling, apoptosis
date published: 2008-03-19
date modified: 2026-07-24T03:31:38Z
provider: National University of Singapore
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: National University of Singapore