The mitochondrial permeability transition: Recent progress and open questions.
FEBS J
; 289(22): 7051-7074, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-34710270
ABSTRACT
Major progress has been made in defining the basis of the mitochondrial permeability transition, a Ca2+ -dependent permeability increase of the inner membrane that has puzzled mitochondrial research for almost 70 years. Initially considered an artefact of limited biological interest by most, over the years the permeability transition has raised to the status of regulator of mitochondrial ion homeostasis and of druggable effector mechanism of cell death. The permeability transition is mediated by opening of channel(s) modulated by matrix cyclophilin D, the permeability transition pore(s) (PTP). The field has received new impulse (a) from the hypothesis that the PTP may originate from a Ca2+ -dependent conformational change of F-ATP synthase and (b) from the reevaluation of the long-standing hypothesis that it originates from the adenine nucleotide translocator (ANT). Here, we provide a synthetic account of the structure of ANT and F-ATP synthase to discuss potential and controversial mechanisms through which they may form high-conductance channels; and review some intriguing findings from the wealth of early studies of PTP modulation that still await an explanation. We hope that this review will stimulate new experiments addressing the many outstanding problems, and thus contribute to the eventual solution of the puzzle of the permeability transition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Necrose Dirigida por Permeabilidade Transmembrânica da Mitocôndria
/
Poro de Transição de Permeabilidade Mitocondrial
Idioma:
En
Revista:
FEBS J
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Itália
País de publicação:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM