ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Cardiolipin remodeling by ALCAT1 links hypoxia to coronary artery disease by promoting mitochondrial dysfunction.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- Integrated Methylome and Transcriptome Analysis in Chronic Chagas Cardiomyopathy Uncovers Alterations in Heart Development.The Journal of infectious diseases · 2026Article
- Mitochondrial lipid remodeling in sepsis-associated acute kidney injury: a cardiolipin-centered convergence framework.Archives of toxicology · 2026Review
- Exercise Improves Mitochondrial Homeostasis: A Potential Neuroprotective Strategy for Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2026Review
- ALCAT1 promotes diabetic cardiomyopathy by linking myocardial tetralinoleoyl cardiolipin deficiency to lipotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- hUCMSC mitochondrial EVs confer neuroprotection after ischemia by Tom1l2-mediated mitochondrial fusion and Crls1-cardiolipin axis reprogramming.Redox biology · 2026Article
- Exercise modulates redox homeostasis in cardiovascular and metabolic diseases: from bench to clinic.Cardiovascular diabetology · 2026Review
- Exploring the effects of moxibustion on pathological remodeling in rats with myocardial ischemia-reperfusion injury based on mitochondrial cardiolipin protection.Frontiers in pharmacology · 2026Article
- Cardiolipin remodelling in mitochondrial therapeutics: translational evidence chains from elamipretide to emerging strategies.Frontiers in physiology · 2026Review
- KIF13B Attenuates Sepsis-Induced Myocardial Dysfunction through the Stabilization of PLIN5.Research (Washington, D.C.) · 2026Article
- Maternal Genotype and Dietary Vitamin A Modify Aortic Arch Phenotypes in a Mouse Model of 22q11DS.International journal of molecular sciences · 2025Article
- Review
- Identification of lipid metabolism-related genes in myocardial infarction: implications for diagnosis and therapy.Journal of cardiothoracic surgery · 2025Article
- Targeting Lp-PLA2 inhibits profibrotic monocyte-derived macrophages in silicosis through restoring cardiolipin-mediated mitophagy.Cellular & molecular immunology · 2025Article
- Aerobic Exercise Alleviates Cardiac Dysfunction Correlated with Lipidomics and Mitochondrial Quality Control.Antioxidants (Basel, Switzerland) · 2025Article
- Total cardiolipin levels in gastric and colon cancer: evaluating the prognostic potential.Lipids in health and disease · 2025Article
- Molecular Mechanism of Aerobic Exercise Ameliorating Myocardial Mitochondrial Injury in Mice with Heart Failure.International journal of molecular sciences · 2025Article
- Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction.Cell death & disease · 2025Article
- Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells.Aging cell · 2025Article
- ALCAT1-Mediated Pathological Cardiolipin Remodeling and PLSCR3-Mediated Cardiolipin Transferring Contribute to LPS-Induced Myocardial Injury.Biomedicines · 2024Article
- In Vitro Hypoxia/Reoxygenation Induces Mitochondrial Cardiolipin Remodeling in Human Kidney Cells.International journal of molecular sciences · 2024Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiolipin is a mitochondrial signature phospholipid that plays a pivotal role in maintaining cardiac health. A loss of tetralinoleoyl cardiolipin (TLCL), the predominant cardiolipin species in the healthy mammalian heart, is implicated in the pathogenesis of coronary heart disease (CHD) through poorly defined mechanisms. Here, we identified acyl-coenzyme A:lysocardiolipin acyltransferase-1 (ALCAT1) as the missing link between hypoxia and CHD in an animal model of myocardial infarction (MI). ALCAT1 is an acyltransferase that promotes mitochondrial dysfunction in aging-related diseases by catalyzing pathological remodeling of cardiolipin. In support of a causative role of ALCAT1 in CHD, we showed that ALCAT1 expression was potently upregulated by MI, linking myocardial hypoxia to oxidative stress, TLCL depletion, and mitochondrial dysfunction. Accordingly, ablation of the ALCAT1 gene or pharmacological inhibition of the ALCAT1 enzyme by Dafaglitapin (Dafa), a potent and highly specific ALCAT1 inhibitor, not only restored TLCL levels but also mitochondrial respiration by attenuating signal transduction pathways mediated by hypoxia-inducible factor 1α (HIF-1α). Consequently, ablation or pharmacological inhibition of ALCAT1 by Dafa effectively mitigated CHD and its underlying pathogenesis, including dilated cardiomyopathy, left ventricle dysfunction, myocardial inflammation, fibrosis, and apoptosis. Together, the findings have provided the first proof-of-concept studies for targeting ALCAT1 as an effective treatment for CHD.
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