ArticleCirculation research2023
Enhanced Mitochondria-SR Tethering Triggers Adaptive Cardiac Muscle Remodeling.
Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 36 citations in OpenAlex.
- Prospective associations of premature senescence, inflammation, and MERCSs in the cardioprotective effect of CBD in HFpEF.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Loss of Rab8a-Dependent Tethering of Lipid Droplets to Mitochondria Contributes to Hypoxia-Reoxygenation Injury.MedComm · 2026Article
- Beyond the Powerhouse: Mitochondrial Crosstalk as a Master Regulator of Cardiac Metabolic Homeostasis and Failure.Journal of cardiovascular translational research · 2026Review
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- Dynamic collaboration between mitochondria and organelles: mechanisms, functions, and disease implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Fumarate hydratase ameliorates pressure overload induced cardiac remodeling by controlling Elovl7-mediated biosynthesis of unsaturated fatty acids.Acta pharmacologica Sinica · 2026Article
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- The Potential Role of Iron Homeostasis and Ferroptosis in Exercise Nutrition and Health.Nutrients · 2026Review
- A guide to characterizing the dynamic mitochondria-endoplasmic reticulum contact sites.The FEBS journal · 2025Review
- The ARVC-5-associated protein TMEM43 controls mitochondrial energy metabolism by stabilising ER-mitochondrial contact sites.Cellular and molecular life sciences : CMLS · 2025Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts.EMBO reports · 2025Article
- Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure.Journal of molecular and cellular cardiology plus · 2025Article
- Sarcoplasmic reticulum-mitochondria microdomains: hugging and kissing in the heart.American journal of physiology. Cell physiology · 2025Review
- Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.Bone research · 2025Review
- Anisotropic Micro/Nanotopography Regulating Mitochondrial Dynamics in Cardiomyocytes.Research (Washington, D.C.) · 2025Article
- Air pollutants as modulators of mitochondrial quality control in cardiovascular disease.Physiological reports · 2024Review
- Mitochondria-Associated Organelle Crosstalk in Myocardial Ischemia/Reperfusion Injury.Journal of cardiovascular translational research · 2024Review
- Quantitative 3D electron microscopy characterization of mitochondrial structure, mitophagy, and organelle interactions in murine atrial fibrillation.Journal of structural biology · 2024Article
- Mitochondrial calcium in cardiac ischemia/reperfusion injury and cardioprotection.Basic research in cardiology · 2024Review
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16 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundCardiac contractile function requires high energy from mitochondria, and Ca
methodsWe introduced to mice a cardiac muscle-specific engineered tether (linker) transgene with a fluorescent protein core and deployed 2D/3D electron microscopy, biochemical approaches, fluorescence imaging, in vivo and ex vivo cardiac performance monitoring and stress challenges to characterize the linker phenotype.
resultsExpressed in the mature cardiomyocytes, the linker expanded and tightened individual mitochondria-junctional SR contacts; but also evoked a marked remodeling with large dense mitochondrial clusters that excluded dyads. Yet, excitation-bioenergetics coupling remained well-preserved, likely due to more longitudinal mitochondria-dyad contacts and nanotunnelling between mitochondria exposed to junctional SR and those sealed away from junctional SR. Remarkably, the linker decreased female vulnerability to acute massive β-adrenergic stress. It also reduced myocyte death and mitochondrial calcium-overload-associated myocardial impairment in ex vivo ischemia/reperfusion injury.
conclusionsWe propose that mitochondria-SR/endoplasmic reticulum contacts operate at a structural optimum. Although acute changes in tethering may cause dysfunction, upon chronic enhancement of contacts from early life, adaptive remodeling of the organelles shifts the system to a new, stable structural optimum. This remodeling balances the individually enhanced mitochondrion-junctional SR crosstalk and excitation-bioenergetics coupling, by increasing the connected mitochondrial pool and, presumably, Ca
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