The mitochondrial permeability transition pore in AD 2016: An update.

Published on Oct 1, 2016in Biochimica et Biophysica Acta: Bioenergetics3.465
· DOI :10.1016/J.BBAMCR.2016.02.012
Lucia Biasutto26
Estimated H-index: 26
(UNIPD: University of Padua),
Michele Azzolini16
Estimated H-index: 16
(UNIPD: University of Padua)
+ 1 AuthorsMario Zoratti56
Estimated H-index: 56
(UNIPD: University of Padua)
Abstract Over the past 30 years the mitochondrial permeability transition – the permeabilization of the inner mitochondrial membrane due to the opening of a wide pore – has progressed from being considered a curious artifact induced in isolated mitochondria by Ca 2 + and phosphate to a key cell-death-inducing process in several major pathologies. Its relevance is by now universally acknowledged and a pharmacology targeting the phenomenon is being developed. The molecular nature of the pore remains to this day uncertain, but progress has recently been made with the identification of the F O F 1 ATP synthase as the probable proteic substrate. Researchers sharing this conviction are however divided into two camps: these believing that only the ATP synthase dimers or oligomers can form the pore, presumably in the contact region between monomers, and those who consider that the ring-forming c subunits in the F O sector actually constitute the walls of the pore. The latest development is the emergence of a new candidate: Spastic Paraplegia 7 (SPG7), a mitochondrial AAA-type membrane protease which forms a 6-stave barrel. This review summarizes recent developments of research on the pathophysiological relevance and on the molecular nature of the mitochondrial permeability transition pore. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
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