ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore.
ATP synthase c-subunit
HAP1-A12 cells
cyclosporine A-sensitive channel
patch-clamp
permeability transition pore
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
02 01 2019
02 01 2019
Historique:
received:
24
04
2018
revised:
01
08
2018
accepted:
06
12
2018
entrez:
4
1
2019
pubmed:
4
1
2019
medline:
20
3
2020
Statut:
ppublish
Résumé
Permeability transition (PT) is an increase in mitochondrial inner membrane permeability that can lead to a disruption of mitochondrial function and cell death. PT is responsible for tissue damage in stroke and myocardial infarction. It is caused by the opening of a large conductance (∼1.5 nS) channel, the mitochondrial PT pore (mPTP). We directly tested the role of the c-subunit of ATP synthase in mPTP formation by measuring channel activity in c-subunit knockout mitochondria. We found that the classic mPTP conductance was lacking in c-subunit knockout mitochondria, but channels sensitive to the PT inhibitor cyclosporine A could be recorded. These channels had a significantly lower conductance compared with the cyclosporine A-sensitive channels detected in parental cells and were sensitive to the ATP/ADP translocase inhibitor bongkrekic acid. We propose that, in the absence of the c-subunit, mPTP cannot be formed, and a distinct cyclosporine A-sensitive low-conductance channel emerges.
Identifiants
pubmed: 30605668
pii: S2211-1247(18)31963-6
doi: 10.1016/j.celrep.2018.12.033
pmc: PMC6521848
mid: NIHMS1517817
pii:
doi:
Substances chimiques
Mitochondrial Membrane Transport Proteins
0
Mitochondrial Permeability Transition Pore
0
Cyclosporine
83HN0GTJ6D
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11-17.e2Subventions
Organisme : NIA NIH HHS
ID : K01 AG054734
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115570
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS081746
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS045876
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS045876
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
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