MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-04-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718304741 |
| id |
doaj-d8a52722cb5c491eaab6dfcbe01c7e01 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 Santhanam Shanmughapriya Jeffrey Caplan Benjamin L. Prosser Donald L. Gill Peter B. Stathopulos Gianluca Gallo David C. Chan Prashant Mishra Muniswamy Madesh |
| spellingShingle |
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 Santhanam Shanmughapriya Jeffrey Caplan Benjamin L. Prosser Donald L. Gill Peter B. Stathopulos Gianluca Gallo David C. Chan Prashant Mishra Muniswamy Madesh MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress Cell Reports |
| author_facet |
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 Santhanam Shanmughapriya Jeffrey Caplan Benjamin L. Prosser Donald L. Gill Peter B. Stathopulos Gianluca Gallo David C. Chan Prashant Mishra Muniswamy Madesh |
| author_sort |
Neeharika Nemani |
| title |
MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress |
| title_short |
MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress |
| title_full |
MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress |
| title_fullStr |
MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress |
| title_full_unstemmed |
MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress |
| title_sort |
miro-1 determines mitochondrial shape transition upon gpcr activation and ca2+ stress |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-04-01 |
| description |
Summary: 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. Keywords: mitochondrial shape, MiST, calcium, Miro, EF hand, PTP, MCU, mitophagy, autophagy, mitochondrial dynamics |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718304741 |
| work_keys_str_mv |
AT neeharikanemani miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT edmundcarvalho miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT dhanendratomar miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT zhiweidong miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT andreaketschek miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT sarahlbreves miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT fabianjana miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT alisonmworth miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT julieheffler miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT palaniappanpalaniappan miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT aparnatripathi miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT ramasamysubbiah miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT massimofriitano miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT ajayseelam miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT thomasmanfred miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT kieitoh miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT shuxiameng miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT hiromisesaki miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT williamjcraigen miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT sudarsanrajan miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT santhanamshanmughapriya miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT jeffreycaplan miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT benjaminlprosser miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT donaldlgill miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT peterbstathopulos miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT gianlucagallo miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT davidcchan miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT prashantmishra miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress AT muniswamymadesh miro1determinesmitochondrialshapetransitionupongpcractivationandca2stress |
| _version_ |
1725162275141058560 |
| spelling |
doaj-d8a52722cb5c491eaab6dfcbe01c7e012020-11-25T01:13:26ZengElsevierCell Reports2211-12472018-04-0123410051019MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ StressNeeharika Nemani0Edmund Carvalho1Dhanendra Tomar2Zhiwei Dong3Andrea Ketschek4Sarah L. Breves5Fabián Jaña6Alison M. Worth7Julie Heffler8Palaniappan Palaniappan9Aparna Tripathi10Ramasamy Subbiah11Massimo F. Riitano12Ajay Seelam13Thomas Manfred14Kie Itoh15Shuxia Meng16Hiromi Sesaki17William J. Craigen18Sudarsan Rajan19Santhanam Shanmughapriya20Jeffrey Caplan21Benjamin L. Prosser22Donald L. Gill23Peter B. Stathopulos24Gianluca Gallo25David C. Chan26Prashant Mishra27Muniswamy Madesh28Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USADepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Molecular and Human Genetics, The Mitochondrial Diagnostic Laboratory, Baylor College of Medicine, Houston, TX 77030, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Biological Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USADepartment of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Cellular and Molecular Physiology, Penn State Hershey College of Medicine, Hershey, PA 17033, USADepartment of Physiology and Pharmacology, Western University, London, ON N6A 5C1, CanadaDepartment of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USAChildren’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Corresponding authorSummary: 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. Keywords: mitochondrial shape, MiST, calcium, Miro, EF hand, PTP, MCU, mitophagy, autophagy, mitochondrial dynamicshttp://www.sciencedirect.com/science/article/pii/S2211124718304741 |