Journal article
MIRO1 Is Required for Dynamic Increases in Mitochondria-ER Contact Sites and Mitochondrial ATP During the Cell Cycle
Cells (Basel, Switzerland), Vol.14(7), 482
03/22/2025
DOI: 10.3390/cells14070482
PMCID: PMC11988184
PMID: 40214436
Abstract
Mitochondria-ER contact sites (MERCS) are vital for mitochondrial dynamics, lipid exchange, Ca2+ homeostasis, and energy metabolism. We examined whether mitochondrial metabolism changes during the cell cycle depend on MERCS dynamics and are regulated by the outer mitochondrial protein mitochondrial rho GTPase 1 (MIRO1). Wound healing was assessed in mice with fibroblast-specific deletion of MIRO1. Wild-type and MIRO1-/- fibroblasts and vascular smooth muscle cells were evaluated for proliferation, cell cycle progression, number of MERCS, distance, and protein composition throughout the cell cycle. Restoration of MIRO1 mutants was used to test the role of MIRO1 domains; Ca2+ transients and mitochondrial metabolism were evaluated using biochemical, immunodetection, and fluorescence techniques. MERCS increased in number during G1/S compared with during G0, which was accompanied by a notable rise in protein–protein interactions involving VDAC1 and IP3R as well as GRP75 and MIRO1 by proximity-ligation assays. Split-GFP ER/mitochondrial contacts of 40 nm also increased. Mitochondrial Ca2+ concentration ([Ca2+]), membrane potential, and ATP levels correlated with the formation of MERCS during the cell cycle. MIRO1 deficiency blocked G1/S progression and the cell-cycle-dependent formation of MERCS and altered ER Ca2+ release and mitochondrial Ca2+ uptake. MIRO1 mutants lacking the Ca2+-sensitive EF hands or the transmembrane domain did not rescue cell proliferation or the formation of MERCS. MIRO1 controls an increase in the number of MERCS during cell cycle progression and increases mitochondrial [Ca2+], driving metabolic activity and proliferation through its EF hands.
Details
- Title: Subtitle
- MIRO1 Is Required for Dynamic Increases in Mitochondria-ER Contact Sites and Mitochondrial ATP During the Cell Cycle
- Creators
- Benney T. Endoni - University of IowaOlha M. Koval - University of IowaChantal Allamargot - University of IowaTara Kortlever - University of IowaLan Qian - University of IowaRiley J. Sadoski - University of IowaDenise Juhr - University of Iowa, Internal MedicineIsabella M. Grumbach - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cells (Basel, Switzerland), Vol.14(7), 482
- DOI
- 10.3390/cells14070482
- PMID
- 40214436
- PMCID
- PMC11988184
- NLM abbreviation
- Cells
- ISSN
- 2073-4409
- eISSN
- 2073-4409
- Publisher
- MDPI
- Grant note
- NIHDepartment of Veterans Affairs: I01 BX000163 American Heart Association: 17GRNT33660032, 22PRE902649
This research was funded in part by grants from the NIH (R01 HL 157956 to IMG and WHT), the Department of Veterans Affairs (I01 BX000163 to IMG), and the American Heart Association (17GRNT33660032 to IMG and 22PRE902649 to BTE). The contents of this article do not represent the views of the Department of Veterans Affairs or the US Government.
- Language
- English
- Date published
- 03/22/2025
- Academic Unit
- Core Research Facilities; Cardiovascular Medicine; Surgery; Radiation Oncology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984802194302771
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