Molecular mechanisms of cell death : central implication of ATP synthase in mitochondrial permeability transition

Bonora, Massimo and Wieckowski, Mariusz R. and Chinopoulos, Christos and Kepp, Oliver and Kroemer, Guido and Galluzzi, Lorenzo and Pinton, Paolo (2014) Molecular mechanisms of cell death : central implication of ATP synthase in mitochondrial permeability transition. ONCOGENE, 2014. in press. ISSN 0950-9232

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The term mitochondrial permeability transition (MPT) is commonly employed to indicate an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes. Widespread MPT has catastrophic consequences for the cell, de facto marking the boundary between cellular life and death. MPT results indeed in the structural and functional collapse of mitochondria, an event that commits cells to suicide via regulated necrosis or apoptosis. MPT plays a central role in the etiology of both acute and chronic diseases characterized by the loss of postmitotic cells. Moreover, cancer cells are often relatively insensitive to the induction of MPT, underlying their increased resistance to potentially lethal cues. Thus, intense efforts have been dedicated not only at the understanding of MPT in mechanistic terms, but also at the development of pharmacological MPT modulators. In this setting, multiple mitochondrial and extramitochondrial proteins have been suspected to critically regulate the MPT. So far, however, only peptidylprolyl isomerase F (PPIF, best known as cyclophilin D) appears to constitute a key component of the socalled permeability transition pore complex (PTPC), the supramolecular entity that is believed to mediate the MPT. Here, after reviewing the structural and functional features of the PTPC, we summarize recent findings suggesting that another of its core components is represented by the c subunit of mitochondrial ATP synthase.

Item Type: Article
Uncontrolled Keywords: adenine nucleotide translocase; autophagy; BCL-2; mitochondrial outer membrane permeabilization; p53; voltage-dependent anion channel.
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
Depositing User: MTMT SWORD
Date Deposited: 17 Mar 2014 13:21
Last Modified: 17 Mar 2014 13:21

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