1.A.129. The Mitochondrial Permeability Transition Pore (mPTP) Family
The mitochondrial permeability transition (mPT) is a phenomenon that abruptly causes the flux of low molecular weight solutes (molecular weight up to 1,500 KDa) across the generally impermeable inner mitochondrial membrane. The mPT is mediated by the so-called mitochondrial permeability transition pore (mPTP), a supramolecular entity assembled at the interface of the inner and outer mitochondrial membranes (Bonora et al. 2022). In contrast to mitochondrial outer membrane permeabilization, which mostly activates apoptosis, mPT can trigger different cellular responses, from the physiological regulation of mitophagy to the activation of apoptosis or necrosis. Although there are several molecular candidates for the mPTP, its molecular nature remains contentious. Experimental evidence has highlighted mitochondrial F1Fo ATP synthase (TC# 3.A.2) as a participant in mPTP formation, although a molecular model for its transition to the mPTP is still lacking. The resolution of the F1Fo ATP synthase structure by cryogenic EM led to a model for mPTP gating. The elusive molecular nature of the mPTP is now being clarified, marking a turning point for understanding mitochondrial biology and its pathophysiological ramifications. Bonora et al. 2022 provide an up-to-date (2022) reference for an understanding of the mammalian mPTP and its cellular functions. Current insights have been obtained into the molecular mechanisms of mPT from studies in vivo or in artificial membranes - on mPTP activity and functions. The contribution of the mPTP to human disease has also been considered (Bonora et al. 2022). Thirty protein constituents and modifiers of the mPTP (see TC#s 1.A.14, 1.B.8, 2.A.29, 3.A.2, etc.) have been tabulated (Bonora et al. 2022).