F‐ATP synthase and the permeability transition pore: fewer doubts, more certainties

Whether the mitochondrial permeability transition pore (PTP), also called mitochondrial megachannel (MMC), originates from the F‐ATP synthase is a matter of controversy. This hypothesis is supported both by site‐directed mutagenesis of specific residues of F‐ATP synthase affecting regulation of the...

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Bibliographic Details
Published in:FEBS letters 2019-07, Vol.593 (13), p.1542-1553
Main Authors: Carraro, Michela, Checchetto, Vanessa, Szabó, Ildikó, Bernardi, Paolo
Format: Article
Language:English
Subjects:
Animals
ATP synthase
calcium
channel
cyclophilin
Humans
mitochondria
Mitochondria - metabolism
Mitochondrial Membrane Transport Proteins - metabolism
Mitochondrial Proton-Translocating ATPases - chemistry
Mitochondrial Proton-Translocating ATPases - genetics
Mitochondrial Proton-Translocating ATPases - metabolism
permeability transition
Protein Engineering
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Summary:Whether the mitochondrial permeability transition pore (PTP), also called mitochondrial megachannel (MMC), originates from the F‐ATP synthase is a matter of controversy. This hypothesis is supported both by site‐directed mutagenesis of specific residues of F‐ATP synthase affecting regulation of the PTP/MMC and by deletion of specific subunits causing dramatic changes in channel conductance. In contrast, human cells lacking an assembled F‐ATP synthase apparently display persistence of the PTP. We discuss recent data that shed new light on this controversy, supporting the conclusion that the PTP/MMC originates from a Ca2+‐dependent conformational change in F‐ATP synthase allowing its reversible transformation into a high‐conductance channel.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.13485