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MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress

Nemani, Neeharika
; ; ; 
Dong, Zhiwei
; 
Ketschek, Andrea
; 
Breves, Sarah L.
; 
Jana, Fabian
; 
Worth, Alison M.
; 
Heffler, Julie
; 
Palaniappan, Palaniappan
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Journal article
Date
2018-04-24
Advisor
Committee member
Group
Shriners Hospital Pediatric Research Center (Temple University)
Center for Translational Medicine (Temple University)
Department
Anatomy and Cell Biology
Medical Genetics and Molecular Biochemistry
Subject
Mitochondrial shape
 MiST
 Calcium
 Miro
 EF hand
 PTP
 MCU
 Mitophagy
 Autophagy
 Mitochondrial dynamics
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http://hdl.handle.net/20.500.12613/8741
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NemaniEtAl-JournalArticle-2018.pdf
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DOI
https://doi.org/10.1016/j.celrep.2018.03.098
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.
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Citation
Nemani et al., 2018, Cell Reports 23, 1005–1019, April 24, 2018 ª 2018 The Author(s). https://doi.org/10.1016/j.celrep.2018.03.098
Citation to related work
Cell Press
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Cell Reports, Vol. 23, Iss. 4
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