| Literature DB >> 29694881 |
Neeharika Nemani1, Edmund Carvalho1, Dhanendra Tomar1, Zhiwei Dong1, Andrea Ketschek2, Sarah L Breves1, Fabián Jaña1, Alison M Worth1, Julie Heffler3, Palaniappan Palaniappan1, Aparna Tripathi1, Ramasamy Subbiah1, Massimo F Riitano1, Ajay Seelam1, Thomas Manfred1, Kie Itoh4, Shuxia Meng5, Hiromi Sesaki4, William J Craigen6, Sudarsan Rajan1, Santhanam Shanmughapriya1, Jeffrey Caplan7, Benjamin L Prosser3, Donald L Gill8, Peter B Stathopulos9, Gianluca Gallo2, David C Chan5, Prashant Mishra10, Muniswamy Madesh11.
Abstract
Mitochondria shape cytosolic calcium ([Ca2+]c) transients and utilize the mitochondrial Ca2+ ([Ca2+]m) in exchange for bioenergetics output. Conversely, dysregulated [Ca2+]c causes [Ca2+]m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca2+ uptake exhibited elevated [Ca2+]c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca2+-induced shape change that is distinct from mitochondrial fission and swelling. [Ca2+]c elevation, but not MCU-mediated Ca2+ uptake, appears to be essential for the process we term mitochondrial shape transition (MiST). MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca2+-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca2+ sensor that decodes metazoan Ca2+ signals as MiST.Entities:
Keywords: EF hand; MCU; MiST; Miro; PTP; autophagy; calcium; mitochondrial dynamics; mitochondrial shape; mitophagy
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Year: 2018 PMID： 29694881 PMCID： PMC5973819 DOI： 10.1016/j.celrep.2018.03.098
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423