Research and Production Center, KORVET, Kryukovo village, building 30, Domodedovo, Moscow region, Russia.
Research Article
World Journal of Advanced Research and Reviews, 2023, 18(02), 825-828
Article DOI: 10.30574/wjarr.2023.18.2.0913
Received on 08 April 2023; revised on 16 May 2023; accepted on 18 May 2023
Mitochondria play a fundamental role in the functioning of the body but are also responsible for dysfunction, apoptosis, and death, associated with the mPTP (mitochondrial permeability transition pore) opening. Despite the fact that there are many articles on this topic, none of them solve the problem of PTP identification. The opening of the PTP is elicited by matrix Ca2+ and stimulated by binding of cyclophilin D (CyPD), Pi, elevated concentration of reactive oxygen species (ROS), free fatty acids, or diminished transmembrane potential. Nucleotides, Mg2+, and the binding of (cyclosporin A) CsA are known molecular inhibitors of PTP opening, whereas arginine-specific adducts of phenylglyoxal modulate PTP opening in a species and net-charge-dependent manner. It seems to us that the reason for the unresolved problem of mPTP lies in ignorance of the functioning of ATP synthase. According to our mechano-chemiosmotic mechanism we suggest that in ATP synthase two channels are connected, consisting of a c-ring of Fо and, α3β3-hexamer with a cap the oligomycin sensitivity conferring protein (OSCP) subunit of F1 in mitochondria closing a c-ring. In our opinion, OSCP subunit together with α3β3-hexamer act as an analogue of adenine nucleotide translocase (ANT), which can be designated as F1-ANT. It exchanges synthesized 3-ATP molecules in the active center of ATP synthase for 3-ADP molecules from the matrix with the participation of sodium and magnesium ions. Thus, we conclude that both ANT in the membrane and F1-ANT (OSCP subunit together with α3β3-hexamer) in the complex with the c-ring of ATP synthase are jointly involved in the functioning of mPTP.
Mechano-chemiosmotic mechanism; Mitochondrial permeability transition pore; OSCP; ANT
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Kasumov E.A, Kasumov R.E and Kasumova I.V. The new vision of mitochondrial permeability transition pore opening. World Journal of Advanced Research and Reviews, 2023, 18(2), 825-828. Article DOI: https://doi.org/10.30574/wjarr.2023.18.2.0913