MITOCHONDRIAL PERMEABILITY TRANSITION PORE: STRUCTURE, PROPERTIES AND ROLE IN CELLULAR PATHOPHYSIOLOGY

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Abstract

The Mitochondrial Permeability Transition pore (MPT pore) activated by Ca2+ ions is a phenomenon that has long been the subject of intense study. Cyclophilin D-dependent opening of the MPT pore in mitochondria in response to calcium overload and oxidative stress leads to swelling of the mitochondrial matrix and depolarization of the inner membrane. These processes are accompanied by a dysregulation of ion homeostasis, damage to mitochondrial membranes and, ultimately, cell death. Despite decades of research, the molecular identity of the MPT pore remains unclear. Recently, its key structural components, along with the regulatory protein cyclophilin D, are considered to be the inner membrane proteins ATP synthase and adenine nucleotide translocator (ANT). The involvement of the MPT pore in the progression of various pathological conditions and diseases, as well as in a number of physiological processes, such as the regulation of cellular bioenergetics and rapid release of Ca2+, is widely discussed. This review summarizes modern molecular genetic data on the putative structure of the MPT pore, traces the evolution of views on its functioning — from the interpretation as a simple experimental artifact to the recognition of a putative key regulator of energy metabolism — and also considers the mechanisms of its regulation and pathophysiological role.

About the authors

K. N. Belosludtsev

Federal State Budgetary Educational Institution of Higher Education "Mari State University"; Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences

Email: bekonik@gmail.com
Yoshkar-Ola, Russia; Pushchino, Russia

M. V. Dubinin

Federal State Budgetary Educational Institution of Higher Education "Mari State University"

Yoshkar-Ola, Russia

N. V. Belosludtseva

Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences

Pushchino, Russia

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