ArticleThe Journal of biological chemistry2015
Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Dapagliflozin sustains heart function in type 3 cardiorenal syndrome by restoring DUSP1-dependent mitochondrial quality control.Acta diabetologica · 2026Article
- Mitochondria associated membranes in dilated cardiomyopathy: connecting pathogenesis and cellular dysfunction.Frontiers in cardiovascular medicine · 2025Review
- Regulation of mitochondrial dynamics in cardiomyocytes: implications for cardiac health and disease.Frontiers in cell and developmental biology · 2025Review
- Dynamin-related protein 1 mediates the therapeutic effect of isoliquiritigenin in diabetic intimal hyperplasia via regulation of mitochondrial fission.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Dysfunctional mitochondria elicit bioenergetic decline in the aged heart.The journal of cardiovascular aging · 2024Article
- The role of mitochondrial dynamics in disease.MedComm · 2023Review
- Review
- Syntaxin 17 Protects Against Heart Failure Through Recruitment of CDK1 to Promote DRP1-Dependent Mitophagy.JACC. Basic to translational science · 2023Article
- Disease-associated mutations in Drp1 have fundamentally different effects on the mitochondrial fission machinery.Human molecular genetics · 2023Article
- Comprehensive Analysis of Mitochondrial Dynamics Alterations in Heart Diseases.International journal of molecular sciences · 2023Review
- The role of mitochondrial fission in cardiovascular health and disease.Nature reviews. Cardiology · 2022Review
- NovelLife science alliance · 2022Article
- Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts.International journal of molecular sciences · 2022Review
- Autophagy in major human diseases.The EMBO journal · 2021Review
- Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice.Communications biology · 2021Article
- Methods to Monitor Mitophagy and Mitochondrial Quality: Implications in Cancer, Neurodegeneration, and Cardiovascular Diseases.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Mitochondrial unfolded protein response, mitophagy and other mitochondrial quality control mechanisms in heart disease and aged heart.Croatian medical journal · 2020Review
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 5 institutions in 3 countries.
Funding
Abstract
We have reported previously that a missense mutation in the mitochondrial fission gene Dynamin-related protein 1 (Drp1) underlies the Python mouse model of monogenic dilated cardiomyopathy. The aim of this study was to investigate the consequences of the C452F mutation on Drp1 protein function and to define the cellular sequelae leading to heart failure in the Python monogenic dilated cardiomyopathy model. We found that the C452F mutation increased Drp1 GTPase activity. The mutation also conferred resistance to oligomer disassembly by guanine nucleotides and high ionic strength solutions. In a mouse embryonic fibroblast model, Drp1 C452F cells exhibited abnormal mitochondrial morphology and defective mitophagy. Mitochondria in C452F mouse embryonic fibroblasts were depolarized and had reduced calcium uptake with impaired ATP production by oxidative phosphorylation. In the Python heart, we found a corresponding progressive decline in oxidative phosphorylation with age and activation of sterile inflammation. As a corollary, enhancing autophagy by exposure to a prolonged low-protein diet improved cardiac function in Python mice. In conclusion, failure of Drp1 disassembly impairs mitophagy, leading to a downstream cascade of mitochondrial depolarization, aberrant calcium handling, impaired ATP synthesis, and activation of sterile myocardial inflammation, resulting in heart failure.
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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.