Abstract
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.
Original language | English (US) |
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Pages (from-to) | 11-17.e2 |
Journal | Cell Reports |
Volume | 26 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2 2019 |
Keywords
- ATP synthase c-subunit
- HAP1-A12 cells
- cyclosporine A-sensitive channel
- patch-clamp
- permeability transition pore
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology