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However, the second messengers linking mitochondrial dysfunction to initiation of mitophagy remain poorly characterized. Here, we show in mammalian and nematode neurons that Opa1 mutations trigger Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent mitophagy. Deletion or expression of mutated Opa1 in mouse retinal ganglion cells and\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    motor neurons lead to mitochondrial dysfunction, increased cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels, and decreased axonal mitochondrial density. Chelation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    restores mitochondrial density in neuronal processes, neuronal function, and viability. Mechanistically, sustained Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels activate calcineurin and AMPK, placed in the same genetic pathway regulating axonal mitochondrial density. Our data reveal that mitophagy in ADOA depends on Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -calcineurin-AMPK signaling cascade.\n                  <\/jats:p>","DOI":"10.1038\/s41418-021-00847-3","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T09:04:54Z","timestamp":1628845494000},"page":"167-177","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy"],"prefix":"10.1038","volume":"29","author":[{"given":"Marta","family":"Zaninello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Palikaras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aggeliki","family":"Sotiriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-1466","authenticated-orcid":false,"given":"Nektarios","family":"Tavernarakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Scorrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"847_CR1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nrn.2017.170","volume":"19","author":"MJ Devine","year":"2018","unstructured":"Devine MJ, Kittler JT. 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