ArticleCellular signalling2018
RhoA regulates Drp1 mediated mitochondrial fission through ROCK to protect cardiomyocytes.
Article in Cellular signalling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 87 citations in OpenAlex.
- RhoA through its various effectors mediate mitochondrial fragmentation in polycystic kidney disease.iScience · 2026Article
- Remodeling of mitochondrial dynamics by metabolic pathways couples to oncogenic growth inScience advances · 2026Article
- Beyond the Pump: Unravelling Immunometabolic Crosstalk and Organelle Dynamics in Sepsis-Induced Cardiomyopathy.Journal of cardiovascular translational research · 2026Article
- AH001: A New Drug Targeting RhoA in Heart Failure.Circulation research · 2026Article
- ROCK signaling at the crossroads of redox stress, mitochondrial dynamics, and metabolic disease.Redox biology · 2026Review
- Regulation of mitochondrial fission by Drp1 in cardiomyopathy: possible mechanisms linking cellular processes to cell death.Molecular biology reports · 2026Review
- Structural insights into Phospholipase Cε activity and regulation.The Journal of biological chemistry · 2026Review
- Cell death forms in myocardial ischemia-reperfusion injury and their potential clinical applications.Molecular and cellular biochemistry · 2026Review
- RHOA regulates mitochondria-ER contact sites through modulation of the VAPB/PTPIP51 tether.Nature communications · 2025Article
- The Glyco-Switch of life: O-GlcNAcylation in cell fate decision.Glycobiology · 2025Review
- FAK modulates glioblastoma stem cell energetics via regulation of glycolysis and glutamine oxidation.Disease models & mechanisms · 2025Article
- RhoA allosterically activates phospholipase Cε via its EF hands.Communications biology · 2025Article
- Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.Molecular biology reports · 2025Review
- Mitochondrial proteins as biomarkers of cellular senescence and age-associated diseases.Aging · 2025Review
- Targeting lactylation reinforces NK cell cytotoxicity within the tumor microenvironment.Nature immunology · 2025Article
- Mitochondrial fission - changing perspectives for future progress.Journal of cell science · 2025Review
- Increased Matrix Stiffness Promotes Slow Muscle Fibre Regeneration After Skeletal Muscle Injury.Journal of cellular and molecular medicine · 2025Article
- Rnd3 protects against doxorubicin-induced cardiotoxicity through inhibition of PANoptosis in a Rock1/Drp1/mitochondrial fission-dependent manner.Cell death & disease · 2025Article
- Rock inhibitors in Alzheimer's disease.Frontiers in aging · 2025Review
- CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis.Renal failure · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac ischemia/reperfusion, loss of blood flow and its subsequent restoration, causes damage to the heart. Oxidative stress from ischemia/reperfusion leads to dysfunction and death of cardiomyocytes, increasing the risk of progression to heart failure. Alterations in mitochondrial dynamics, in particular mitochondrial fission, have been suggested to play a role in cardioprotection from oxidative stress. We tested the hypothesis that activation of RhoA regulates mitochondrial fission in cardiomyocytes. Our studies show that expression of constitutively active RhoA in cardiomyocytes increases phosphorylation of Dynamin-related protein 1 (Drp1) at serine-616, and leads to localization of Drp1 at mitochondria. Both responses are blocked by inhibition of Rho-associated Protein Kinase (ROCK). Endogenous RhoA activation by the GPCR agonist sphingosine-1-phosphate (S1P) also increases Drp1 phosphorylation and its mitochondrial translocation in a RhoA and ROCK dependent manner. Consistent with the role of mitochondrial Drp1 in fission, RhoA activation in cardiomyocytes leads to formation of smaller mitochondria and this is attenuated by inhibition of ROCK, by siRNA knockdown of Drp1 or by expression of a phosphorylation-deficient Drp1 S616A mutant. In addition, activation of RhoA prevents cell death in cardiomyocytes challenged by oxidative stress and this protection is blocked by siRNA knockdown of Drp1 or by Drp1 S616A expression. Taken together our findings demonstrate that RhoA activation can regulate Drp1 to induce mitochondrial fission and subsequent cellular protection, implicating regulation of fission as a novel mechanism contributing to RhoA-mediated cardioprotection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.