The mitochondrial permeability transition (MPT) consists of an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes, resulting in the osmotic breakout of the organelle. MPT drives cell death and provides an etiological contribution to several human disorders characterized by the acute loss of post-mitotic cells. These conditions include ischemia/reperfusion injury, cancer and neurodegenerative disorders. However, precise knowledge of the structure and regulators of the supramolecular entity that induces MPT, the so-called permeability transition pore complex (PTPC), is lacking and this constitutes a substantial obstacle in the development of MPT-targeting agents with clinical applications. Here we report the current evidences about molecular structure and regulatory components of PTPC. In particular we pay attention on new two proteins which recently were added to the list of PTPC components: the mitochondrial F1FO ATP synthase, particularly and the SPG7 paraplegin matrix AAA peptidase subunit. At least a detailed overview of MPT contribution to pathological condition is provided, focusing on the idea that to develop therapeutic drugs, it will be fundamental to understand the molecular composition of the PTPC.

The Mitochondrial Permeability Transition Pore

Morganti, Claudia
Primo
;
Bonora, Massimo
Secondo
;
Sbano, Luigi;Morciano, Giampaolo;Aquila, Giorgio;Campo, Gianluca;Giorgi, Carlotta
Penultimo
;
Pinton, Paolo
Ultimo
2018

Abstract

The mitochondrial permeability transition (MPT) consists of an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes, resulting in the osmotic breakout of the organelle. MPT drives cell death and provides an etiological contribution to several human disorders characterized by the acute loss of post-mitotic cells. These conditions include ischemia/reperfusion injury, cancer and neurodegenerative disorders. However, precise knowledge of the structure and regulators of the supramolecular entity that induces MPT, the so-called permeability transition pore complex (PTPC), is lacking and this constitutes a substantial obstacle in the development of MPT-targeting agents with clinical applications. Here we report the current evidences about molecular structure and regulatory components of PTPC. In particular we pay attention on new two proteins which recently were added to the list of PTPC components: the mitochondrial F1FO ATP synthase, particularly and the SPG7 paraplegin matrix AAA peptidase subunit. At least a detailed overview of MPT contribution to pathological condition is provided, focusing on the idea that to develop therapeutic drugs, it will be fundamental to understand the molecular composition of the PTPC.
978-3-319-73343-2
978-3-319-73344-9
Mitochondrial permeability transition; Permeability transition pore complex; F1FO ATP synthase; Mitochondrial disorders
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2386866
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