ArticleJCI insight2021
Acetylation of muscle creatine kinase negatively impacts high-energy phosphotransfer in heart failure.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Sex-specific benefits of a combined supplementation of B vitamins, nicotinamide riboside, folate and cobalamin, in a murine model of heart failure.Biology of sex differences · 2025Article
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
- Mechano-energetic uncoupling in heart failure.Nature reviews. Cardiology · 2025Review
- The SIRT1 activator SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery.Cell death & disease · 2025Article
- CKMT1B regulates the proliferation, migration, invasion, and apoptosis of colorectal cancer cells through the AKT/mTOR/STAT3 pathway.Molecular genetics and genomics : MGG · 2025Article
- Impact of ITH on PRAD patients and feasibility analysis of the positive correlation gene MYLK2 applied to PRAD treatment.Frontiers in genetics · 2025Article
- Mitochondrial Dysfunction as a Potential Mechanism Mediating Cardiac Comorbidities in Parkinson's Disease.International journal of molecular sciences · 2024Review
- NAD metabolism and heart failure: Mechanisms and therapeutic potentials.Journal of molecular and cellular cardiology · 2024Review
- Proteomic profiling of prostate cancer reveals molecular signatures under antiandrogen treatment.Clinical proteomics · 2024Article
- Maintaining energy provision in the heart: the creatine kinase system in ischaemia-reperfusion injury and chronic heart failure.Clinical science (London, England : 1979) · 2024Review
- Acetyltransferase in cardiovascular disease and aging.The journal of cardiovascular aging · 2024Article
- Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges.Nature reviews. Cardiology · 2023Review
- Metabolite signaling in the heart.Nature cardiovascular research · 2023Review
- Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Alterations of Lysine Acetylation Profile in Murine Skeletal Muscles Upon Exercise.Frontiers in aging neuroscience · 2022Article
- Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction.Genetics research · 2022Review
- Cardiac Energy Metabolism in Heart Failure.Circulation research · 2021Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
A hallmark of impaired myocardial energetics in failing hearts is the downregulation of the creatine kinase (CK) system. In heart failure patients and animal models, myocardial phosphocreatine content and the flux of the CK reaction are negatively correlated with the outcome of heart failure. While decreased CK activity is highly reproducible in failing hearts, the underlying mechanisms remains elusive. Here, we report an inverse relationship between the activity and acetylation of CK muscle form (CKM) in human and mouse failing hearts. Hyperacetylation of recombinant CKM disrupted MM homodimer formation and reduced enzymatic activity, which could be reversed by sirtuin 2 treatment. Mass spectrometry analysis identified multiple lysine residues on the MM dimer interface, which were hyperacetylated in the failing hearts. Molecular modeling of CK MM homodimer suggested that hyperacetylation prevented dimer formation through interfering salt bridges within and between the 2 monomers. Deacetylation by sirtuin 2 reduced acetylation of the critical lysine residues, improved dimer formation, and restored CKM activity from failing heart tissue. These findings reveal a potentially novel mechanism in the regulation of CK activity and provide a potential target for improving high-energy phosphoryl transfer in heart failure.
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Registered trials
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