The mitochondrial permeability transition pore in AD 2016: An update

Publication date: Available online 21 February 2016
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Lucia Biasutto, Michele Azzolini, Ildikò Szabò, Mario Zoratti
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 Ca²⁺ 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 FOF1 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 FO 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.



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