p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis

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p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis

Ischemia-associated oxidative damage leading to necrosis is a major cause of catastrophic tissue loss, and elucidating its signaling mechanism is therefore of paramount importance. p53 is a central stress sensor responding to multiple insults, including oxidative stress to orchestrate apoptotic and autophagic cell death. Whether p53 can also activate oxidative stress-induced necrosis is, howeve...

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The mitochondrial permeability transition pore.

This chapter reviews recent advances in the identification of the structural elements of the permeability transition pore. The discovery that cyclosporin A (CsA) inhibits the pore proved instrumental. Various approaches indicate that CsA blocks the pore by binding to cyclophilin (CyP)-D. In particular, covalent labelling of CyP-D in situ by a photoactive CsA derivative has shown that pore ligan...

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Diazoxide Opens the Mitochondrial Permeability Transition Pore and Alters Ca Transients in Rat Ventricular Myocytes

Background—The mitochondrial KATP channel (mitoKATP) has been implicated as an end effector or trigger of ischemic preconditioning (IP). Although a mitoKATP opener, diazoxide, mimics IP, mechanisms for the cardioprotective action remain unclear. Methods and Results—We measured Ca transients (CaTs) and mitochondrial inner membrane potential ( m) with confocal microscopy and the fluorescent probe...

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Diazoxide opens the mitochondrial permeability transition pore and alters Ca2+ transients in rat ventricular myocytes.

BACKGROUND The mitochondrial K(ATP) channel (mitoK(ATP)) has been implicated as an end effector or trigger of ischemic preconditioning (IP). Although a mitoK(ATP) opener, diazoxide, mimics IP, mechanisms for the cardioprotective action remain unclear. METHODS AND RESULTS We measured Ca2+ transients (CaTs) and mitochondrial inner membrane potential (Deltapsi(m)) with confocal microscopy and th...

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Erratum to: The Mitochondrial Permeability Transition Pore and ATP Synthase.

Mitochondrial ATP generation by oxidative phosphorylation combines the stepwise oxidation by the electron transport chain (ETC) of the reducing equivalents NADH and FADH2 with the generation of ATP by the ATP synthase. Recent studies show that the ATP synthase is not only essential for the generation of ATP but may also contribute to the formation of the mitochondrial permeability transition po...

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ژورنال

عنوان ژورنال: Cell

سال: 2012

ISSN: 0092-8674

DOI: 10.1016/j.cell.2012.05.014