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L‐ OPA 1 regulates mitoflash biogenesis independently from membrane fusion
Author(s) -
Rosselin Ma,
SantoDomingo Jaime,
Bermont Flavien,
Giacomello Marta,
Demaurex Nicolas
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201642931
Subject(s) - library science , humanities , computer science , art
Mitochondrial flashes mediated by optic atrophy 1 ( OPA 1) fusion protein are bioenergetic responses to stochastic drops in mitochondrial membrane potential (Δψ m ) whose origin is unclear. Using structurally distinct genetically encoded pH ‐sensitive probes, we confirm that flashes are matrix alkalinization transients, thereby establishing the pH nature of these events, which we renamed “mitopHlashes”. Probes located in cristae or intermembrane space as verified by electron microscopy do not report pH changes during Δψ m drops or respiratory chain inhibition. Opa1 ablation does not alter Δψ m fluctuations but drastically decreases the efficiency of mitopHlash/Δψ m coupling, which is restored by re‐expressing fusion‐deficient OPA 1 K301A and preserved in cells lacking the outer‐membrane fusion proteins MFN 1/2 or the OPA 1 proteases OMA 1 and YME 1L, indicating that mitochondrial membrane fusion and OPA 1 proteolytic processing are dispensable. pH /Δψ m uncoupling occurs early during staurosporine‐induced apoptosis and is mitigated by OPA 1 overexpression, suggesting that OPA 1 maintains mitopHlash competence during stress conditions. We propose that OPA 1 stabilizes respiratory chain supercomplexes in a conformation that enables respiring mitochondria to compensate a drop in Δψ m by an explosive matrix pH flash.