@article {27003,
	title = {Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy},
	journal = {Cell Death Differ},
	year = {2021},
	note = {Zaninello, MartaPalikaras, KonstantinosSotiriou, AggelikiTavernarakis, NektariosScorrano, LucaengGA695190/EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))GA737599/EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)GGP15091/Fondazione Telethon (Telethon Foundation)GGP19089/Fondazione Telethon (Telethon Foundation)EnglandCell Death Differ. 2021 Aug 13. pii: 10.1038/s41418-021-00847-3. doi: 10.1038/s41418-021-00847-3.},
	month = {Aug 13},
	edition = {2021/08/15},
	abstract = {Mitochondrial dysfunction and mitophagy are often hallmarks of neurodegenerative diseases such as autosomal dominant optic atrophy (ADOA) caused by mutations in the key mitochondrial dynamics protein optic atrophy 1 (Opa1). 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(2+)-dependent mitophagy. Deletion or expression of mutated Opa1 in mouse retinal ganglion cells and Caenorhabditis elegans motor neurons lead to mitochondrial dysfunction, increased cytosolic Ca(2+) levels, and decreased axonal mitochondrial density. Chelation of Ca(2+) restores mitochondrial density in neuronal processes, neuronal function, and viability. Mechanistically, sustained Ca(2+) 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(2+)-calcineurin-AMPK signaling cascade.},
	isbn = {1476-5403 (Electronic)1350-9047 (Linking)},
	author = {Zaninello, M. and Palikaras, K. and Sotiriou, A. and Tavernarakis, N. and Scorrano, L.}
}
