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Title: Role and regulation of mitochondrial permeability transition in cell death
Keywords: mitochondrial permeability transition, cytochrome c, OPA1, cyclophilin-D, cristae remodeling, apoptosis
Issue Date: 19-Mar-2008
Citation: ZHANG DAWEI (2008-03-19). Role and regulation of mitochondrial permeability transition in cell death. ScholarBank@NUS Repository.
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.
Appears in Collections:Ph.D Theses (Open)

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