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Using structurally distinct genetically encoded pH\u2010sensitive probes, we confirm that flashes are matrix alkalinization transients, thereby establishing the pH nature of these events, which we renamed \u201cmitopHlashes\u201d. Probes located in cristae or intermembrane space as verified by electron microscopy do not report pH changes during \u0394\u03c8\n                    <jats:sub>m<\/jats:sub>\n                    drops or respiratory chain inhibition.\n                    <jats:italic>Opa1<\/jats:italic>\n                    ablation does not alter \u0394\u03c8\n                    <jats:sub>m<\/jats:sub>\n                    fluctuations but drastically decreases the efficiency of mitopHlash\/\u0394\u03c8\n                    <jats:sub>m<\/jats:sub>\n                    coupling, which is restored by re\u2010expressing fusion\u2010deficient OPA1\n                    <jats:sup>K301A<\/jats:sup>\n                    and preserved in cells lacking the outer\u2010membrane fusion proteins MFN1\/2 or the OPA1 proteases OMA1 and YME1L, indicating that mitochondrial membrane fusion and OPA1 proteolytic processing are dispensable. pH\/\u0394\u03c8\n                    <jats:sub>m<\/jats:sub>\n                    uncoupling occurs early during staurosporine\u2010induced apoptosis and is mitigated by OPA1 overexpression, suggesting that OPA1 maintains mitopHlash competence during stress conditions. We propose that OPA1 stabilizes respiratory chain supercomplexes in a conformation that enables respiring mitochondria to compensate a drop in \u0394\u03c8\n                    <jats:sub>m<\/jats:sub>\n                    by an explosive matrix pH flash.\n                  <\/jats:p>","DOI":"10.15252\/embr.201642931","type":"journal-article","created":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T20:10:25Z","timestamp":1486498225000},"page":"451-463","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["L\u2010OPA1 regulates mitoflash biogenesis independently from membrane fusion"],"prefix":"10.1038","volume":"18","author":[{"given":"Manon","family":"Rosselin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Santo\u2010Domingo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavien","family":"Bermont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Giacomello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-6772","authenticated-orcid":false,"given":"Nicolas","family":"Demaurex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,7]]},"reference":[{"key":"BFEMBR201642931_CR1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1146\/annurev.bi.54.070185.005055","volume":"54","author":"Y Hatefi","year":"1985","unstructured":"Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. 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