ArticleCirculation research2020
Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction.
Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
172 citing papers in PubMed, 243 citations in OpenAlex.
- Mitochondrial Fusion and Fission in Age-Related Cardio-Cerebral Diseases: Mechanisms and Interventions.Aging cell · 2026Review
- FTSJ3-Mediated 2'-O-Methylation of HSPA5 mRNA Stabilizes BOP1 via SUMOylation to Drive DRP1-Dependent Mitochondrial Fission and Fatty Acid Oxidation in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pentose phosphate pathway-derived NADPH facilitates physiological hypertrophy and alleviates ischemia-reperfusion injury in the heart.Nature metabolism · 2026Article
- Post-translational modifications of mitochondrion-related proteins: integrative orchestrators of cell fate networks in cardiovascular disease.Cell communication and signaling : CCS · 2026Review
- MMP7-Triggered mitophagy by regulating parkin-mediated ubiquitination of VDAC1 confers anoikis resistance in the epithelium of hyperplastic prostate.Cell death & disease · 2026Article
- CPT1A drives cisplatin resistance via acetylation‑dependent activation of DRP1 and mitochondrial fission in small cell lung cancer.Cell death & disease · 2026Article
- ALCAT1 promotes diabetic cardiomyopathy by linking myocardial tetralinoleoyl cardiolipin deficiency to lipotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Excessive ER-mitochondria coupling: A DRP1-driven mechanism underlying mitochondrial dysfunction and impaired autophagy in stress-induced depression-like behavior in mice.Redox biology · 2026Article
- Growth differentiation factor 15 mitigates lipotoxic steatosis by preserving mitochondrial morphodynamics and augmenting fatty acid oxidation in hepatocytes and liver organoids.Diabetes, obesity & metabolism · 2026Article
- Regulation of mitochondrial fission by Drp1 in cardiomyopathy: possible mechanisms linking cellular processes to cell death.Molecular biology reports · 2026Review
- Mitochondrial Fission and Fusion Disorders and Autophagy Abnormalities in Parkinson's Disease.Neurochemical research · 2026Review
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- The role and therapeutic potential of succinate and succinylation in cardiovascular diseases.Clinical epigenetics · 2026Review
- Pyruvate metabolism enzyme Dlat induces mitochondria protein hyperacetylation to limit fatty acid oxidation in the HFpEF heart.Nature communications · 2026Article
- Article
- Integrative insights into fatty acid metabolism in diabetic cardiomyopathy: From molecular mechanisms to therapeutic strategies.iScience · 2026Review
- Bridging tradition and modernity: mitochondrial dynamics as a Traditional Chinese Medicine therapeutic target in cardiovascular disease.Chinese medicine · 2026Review
- The interplay between circadian rhythm components and apoptosis in health and disease.Human cell · 2026Review
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Mommy issues: how maternal diet shapes offspring mitochondrial physiology.Journal of animal science · 2026Review
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
rationaleLipid overload-induced heart dysfunction is characterized by cardiomyocyte death, myocardial remodeling, and compromised contractility, but the impact of excessive lipid supply on cardiac function remains poorly understood.
objectiveTo investigate the regulation and function of the mitochondrial fission protein Drp1 (dynamin-related protein 1) in lipid overload-induced cardiomyocyte death and heart dysfunction. METHODS AND
resultsMice fed a high-fat diet (HFD) developed signs of obesity and type II diabetes mellitus, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and hypertension. HFD for 18 weeks also induced heart hypertrophy, fibrosis, myocardial insulin resistance, and cardiomyocyte death. HFD stimulated mitochondrial fission in mouse hearts. Furthermore, HFD increased the protein level, phosphorylation (at the activating serine 616 sites), oligomerization, mitochondrial translocation, and GTPase activity of Drp1 in mouse hearts, indicating that Drp1 was activated. Monkeys fed a diet high in fat and cholesterol for 2.5 years also exhibited myocardial damage and Drp1 activation in the heart. Interestingly, HFD decreased nicotinamide adenine dinucleotide (oxidized) levels and increased Drp1 acetylation in the heart. In adult cardiomyocytes, palmitate increased Drp1 acetylation, phosphorylation, and protein levels, and these increases were abolished by restoration of the decreased nicotinamide adenine dinucleotide (oxidized) level. Proteomics analysis and in vitro screening revealed that Drp1 acetylation at lysine 642 (K642) was increased by HFD in mouse hearts and by palmitate incubation in cardiomyocytes. The nonacetylated Drp1 mutation (K642R) attenuated palmitate-induced Drp1 activation, its interaction with voltage-dependent anion channel 1, mitochondrial fission, contractile dysfunction, and cardiomyocyte death.
conclusionsThese findings uncover a novel mechanism that contributes to lipid overload-induced heart hypertrophy and dysfunction. Excessive lipid supply created an intracellular environment that facilitated Drp1 acetylation, which, in turn, increased its activity and mitochondrial translocation, resulting in cardiomyocyte dysfunction and death. Thus, Drp1 may be a critical mediator of lipid overload-induced heart dysfunction as well as a potential target for therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.