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

Neeharika Nemani, Edmund Carvalho, Dhanendra Tomar, Zhiwei Dong, Andrea Ketschek, Sarah L. Breves, Fabián Jaña, Alison M. Worth, Julie Heffler, Palaniappan Palaniappan, Aparna Tripathi, Ramasamy Subbiah, Massimo F. Riitano, Ajay Seelam, Thomas Manfred, Kie Itoh, Shuxia Meng, Hiromi Sesaki, William J. Craigen, Sudarsan Rajan & 9 others Shanmughapriya Santhanam, Jeffrey Caplan, Benjamin L. Prosser, Donald Gill, Peter B. Stathopulos, Gianluca Gallo, David C. Chan, Prashant Mishra, Muniswamy Madesh

Research output: Contribution to journalArticle

8 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)1005-1019
Number of pages15
JournalCell Reports
Volume23
Issue number4
DOIs
StatePublished - Apr 24 2018

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Mitochondria
Mitochondrial Degradation
Mitochondrial Dynamics
Chemical activation
Autophagy
Cell death
Swelling
Cell Death
Mitochondrial Swelling
EF Hand Motifs
Mitochondrial Proteins
Sensors
Tubulin
Ablation
Quality Control
Energy Metabolism
Quality control
Permeability
Calcium

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nemani, N., Carvalho, E., Tomar, D., Dong, Z., Ketschek, A., Breves, S. L., ... Madesh, M. (2018). MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress. Cell Reports, 23(4), 1005-1019. https://doi.org/10.1016/j.celrep.2018.03.098
Nemani, Neeharika ; Carvalho, Edmund ; Tomar, Dhanendra ; Dong, Zhiwei ; Ketschek, Andrea ; Breves, Sarah L. ; Jaña, Fabián ; Worth, Alison M. ; Heffler, Julie ; Palaniappan, Palaniappan ; Tripathi, Aparna ; Subbiah, Ramasamy ; Riitano, Massimo F. ; Seelam, Ajay ; Manfred, Thomas ; Itoh, Kie ; Meng, Shuxia ; Sesaki, Hiromi ; Craigen, William J. ; Rajan, Sudarsan ; Santhanam, Shanmughapriya ; Caplan, Jeffrey ; Prosser, Benjamin L. ; Gill, Donald ; Stathopulos, Peter B. ; Gallo, Gianluca ; Chan, David C. ; Mishra, Prashant ; Madesh, Muniswamy. / MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress. In: Cell Reports. 2018 ; Vol. 23, No. 4. pp. 1005-1019.
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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. 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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Nemani, N, Carvalho, E, Tomar, D, Dong, Z, Ketschek, A, Breves, SL, Jaña, F, Worth, AM, Heffler, J, Palaniappan, P, Tripathi, A, Subbiah, R, Riitano, MF, Seelam, A, Manfred, T, Itoh, K, Meng, S, Sesaki, H, Craigen, WJ, Rajan, S, Santhanam, S, Caplan, J, Prosser, BL, Gill, D, Stathopulos, PB, Gallo, G, Chan, DC, Mishra, P & Madesh, M 2018, 'MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress', Cell Reports, vol. 23, no. 4, pp. 1005-1019. https://doi.org/10.1016/j.celrep.2018.03.098

MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress. / Nemani, Neeharika; Carvalho, Edmund; Tomar, Dhanendra; Dong, Zhiwei; Ketschek, Andrea; Breves, Sarah L.; Jaña, Fabián; Worth, Alison M.; Heffler, Julie; Palaniappan, Palaniappan; Tripathi, Aparna; Subbiah, Ramasamy; Riitano, Massimo F.; Seelam, Ajay; Manfred, Thomas; Itoh, Kie; Meng, Shuxia; Sesaki, Hiromi; Craigen, William J.; Rajan, Sudarsan; Santhanam, Shanmughapriya; Caplan, Jeffrey; Prosser, Benjamin L.; Gill, Donald; Stathopulos, Peter B.; Gallo, Gianluca; Chan, David C.; Mishra, Prashant; Madesh, Muniswamy.

In: Cell Reports, Vol. 23, No. 4, 24.04.2018, p. 1005-1019.

Research output: Contribution to journalArticle

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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 - Santhanam, Shanmughapriya

AU - Caplan, Jeffrey

AU - Prosser, Benjamin L.

AU - Gill, Donald

AU - Stathopulos, Peter B.

AU - Gallo, Gianluca

AU - Chan, David C.

AU - Mishra, Prashant

AU - Madesh, Muniswamy

PY - 2018/4/24

Y1 - 2018/4/24

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Nemani N, Carvalho E, Tomar D, Dong Z, Ketschek A, Breves SL et al. MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress. Cell Reports. 2018 Apr 24;23(4):1005-1019. https://doi.org/10.1016/j.celrep.2018.03.098