TY - JOUR
T1 - MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress
AU - Nemani, Neeharika
AU - Carvalho, Edmund
AU - Tomar, Dhanendra
AU - Dong, Zhiwei
AU - Ketschek, Andrea
AU - Breves, Sarah L.
AU - Jaña, Fabián
AU - Worth, Alison M.
AU - Heffler, Julie
AU - Palaniappan, Palaniappan
AU - Tripathi, Aparna
AU - Subbiah, Ramasamy
AU - Riitano, Massimo F.
AU - Seelam, Ajay
AU - Manfred, Thomas
AU - Itoh, Kie
AU - Meng, Shuxia
AU - Sesaki, Hiromi
AU - Craigen, William J.
AU - Rajan, Sudarsan
AU - Shanmughapriya, Santhanam
AU - Caplan, Jeffrey
AU - Prosser, Benjamin L.
AU - Gill, Donald L.
AU - Stathopulos, Peter B.
AU - Gallo, Gianluca
AU - Chan, David C.
AU - Mishra, Prashant
AU - Madesh, Muniswamy
N1 - Publisher Copyright:
© 2018 The Author(s)
PY - 2018/4/24
Y1 - 2018/4/24
N2 - 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. Metazoan Ca2+ signal determines mitochondrial shape transition (MiST) and cellular quality control. Nemani et al. find that mitochondria undergo shape changes upon Ca2+ stress. MiST is distinct from matrix Ca2+-induced swelling and mitochondrial dynamics. The conserved Ca2+ sensor Miro1 enables MiST and promotes autophagy/mitophagy.
AB - 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. Metazoan Ca2+ signal determines mitochondrial shape transition (MiST) and cellular quality control. Nemani et al. find that mitochondria undergo shape changes upon Ca2+ stress. MiST is distinct from matrix Ca2+-induced swelling and mitochondrial dynamics. The conserved Ca2+ sensor Miro1 enables MiST and promotes autophagy/mitophagy.
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U2 - 10.1016/j.celrep.2018.03.098
DO - 10.1016/j.celrep.2018.03.098
M3 - Article
C2 - 29694881
AN - SCOPUS:85045578026
SN - 2211-1247
VL - 23
SP - 1005
EP - 1019
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -