ArticleCirculation research2012
Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
219 citing papers in PubMed, 1 synthesis or guideline pooled it, 336 citations in OpenAlex.
- Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection.Basic research in cardiology · 2018Guideline
- Mitochondrial fusion is frequent in skeletal muscle and supports excitation-contraction coupling.The Journal of cell biology · 2014Trial
- Inhibition of RBM25 preserves cardiac mitochondrial homeostasis and attenuates ischemic heart failure.Journal of molecular histology · 2026Article
- Review
- Beat-locked ATP microdomains in the sinoatrial node map a Ca2+-timed energetic hierarchy and regional pacemaker roles.The Journal of general physiology · 2026Article
- Demonstration of beat-to-beat, on-demand ATP synthesis in ventricular myocytes reveals sex-specific mitochondrial and cytosolic dynamics.The Journal of physiology · 2026Article
- Disrupted SR-Mitochondria Coupling Drives Ischemia-Reperfusion Vulnerability in the Middle-Aged Rat Heart.Biomedicines · 2026Article
- Energetic microdomains and the vascular control of neuronal and muscle excitability: Toward a unified model.The Journal of physiology · 2026Review
- MAMs-Mediated Calcium Homeostasis in the Pathophysiology of Cardiovascular Diseases: A Mini-Review.Drug design, development and therapy · 2026Review
- Mitochondrial remodeling in heart failure with reduced ejection fraction.Frontiers in physiology · 2026Review
- Identification of MFN2 and NCL as cardiac biomarkers for post-mortem diagnosis of atypical electrocution death.International journal of legal medicine · 2026Article
- Cardiac SR-Mitochondria Contacts-Impact on Cardiac Physiology and Mitochondrial Fitness.Cells · 2025Review
- Article
- Myocardial disarray drives metabolic inefficiency in human cardiomyocytes.Communications biology · 2025Article
- Mechano-energetic uncoupling in heart failure.Nature reviews. Cardiology · 2025Review
- Nonstructural Roles of Junctophilin-2 in the Heart.JACC. Basic to translational science · 2025Review
- Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure.Journal of molecular and cellular cardiology plus · 2025Article
- Article
- Sarcoplasmic reticulum-mitochondria microdomains: hugging and kissing in the heart.American journal of physiology. Cell physiology · 2025Review
- Mitochondrial quality control as a therapeutic target in cardiovascular disease: Mechanistic insights and future directions.Journal of translational internal medicine · 2025Article
159 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
rationaleMitochondrial Ca(2+) uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association of mitochondria to the sarcoplasmic reticulum (SR) may explain efficient mitochondrial Ca(2+) uptake despite low Ca(2+) affinity of the mitochondrial Ca(2+) uniporter. However, the existence of such mitochondrial Ca(2+) microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic reticulum to mitochondria in noncardiac cells.
objectiveTo elucidate roles for Mfn1 and 2 in SR-mitochondrial tethering, Ca(2+) signaling, and bioenergetic regulation in cardiac myocytes. METHODS AND
resultsFruit fly heart tubes deficient of the Drosophila Mfn ortholog MARF had increased contraction-associated and caffeine-sensitive Ca(2+) release, suggesting a role for Mfn in SR Ca(2+) handling. Whereas cardiac-specific Mfn1 ablation had no effects on murine heart function or Ca(2+) cycling, Mfn2 deficiency decreased cardiomyocyte SR-mitochondrial contact length by 30% and reduced the content of SR-associated proteins in mitochondria-associated membranes. This was associated with decreased mitochondrial Ca(2+) uptake (despite unchanged mitochondrial membrane potential) but increased steady-state and caffeine-induced SR Ca(2+) release. Accordingly, Ca(2+)-induced stimulation of Krebs cycle dehydrogenases during β-adrenergic stimulation was hampered in Mfn2-KO but not Mfn1-KO myocytes, evidenced by oxidation of the redox states of NAD(P)H/NAD(P)(+) and FADH(2)/FAD.
conclusionsPhysical tethering of SR and mitochondria via Mfn2 is essential for normal interorganelle Ca(2+) signaling in the myocardium, consistent with a requirement for SR-mitochondrial Ca(2+) signaling through microdomains in the cardiomyocyte bioenergetic feedback response to physiological stress.
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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.