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Heart failure (HF) occurs frequently among older individuals, and dysfunction of cardiac mitochondria is often observed. We here show the cardiac-specific downregulation of a certain mitochondrial component during the chronological aging of mice, which is detrimental to the heart. MitoNEET is a mitochondrial outer membrane protein, encoded by CDGSH iron sulfur domain 1 (CISD1). Expression of mitoNEET was specifically downregulated in the heart and kidney of chronologically aged mice. Mice with a constitutive cardiac-specific deletion of CISD1 on the C57BL/6J background showed cardiac dysfunction only after 12 months of age and developed HF after 16 months; whereas irregular morphology and higher levels of reactive oxygen species in their cardiac mitochondria were observed at earlier time points. Our results suggest a possible mechanism by which cardiac mitochondria may gradually lose their integrity during natural aging, and shed light on an uncharted molecular basis closely related to age-associated HF.
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http://dx.doi.org/10.1038/s42003-021-01675-4 | DOI Listing |
Eur J Heart Fail
September 2025
School of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Aims: Skeletal muscle energetic augmentation might be a mechanism via which intravenous iron improves symptoms in heart failure, but no direct measurement of intrinsic mitochondrial function has been performed to support this notion. This molecular substudy of the FERRIC-HF II trial tested the hypothesis that ferric derisomaltose (FDI) would improve electron transport chain activity, given its high dependence on iron-sulfur clusters which facilitate electron transfer during oxidative phosphorylation.
Methods And Results: Vastus lateralis skeletal muscle biopsies were taken before and 2 weeks after randomization.
Compr Physiol
October 2025
School of Pharmacy and Medical Sciences, Griffith University, Southport, Queensland, Australia.
Mechanisms underlying cardiovascular, affective, and metabolic (CAM) multimorbidity are incompletely defined. We assessed how two risk factors-chronic stress (CS) and a Western diet (WD)-interact to influence cardiovascular function, resilience, adaptability, and allostatic load (AL); explore pathway involvement; and examine relationships with behavioral, metabolic, and systemic AL. Male C57Bl/6 mice (8 weeks old, n = 64) consumed a control (CD) or WD (12%-65%-23% or 32%-57%-11% calories from fat-carbohydrate-protein) for 17 weeks, with half subjected to 2 h daily restraint stress over the final 2 weeks (CD + CS and WD + CS).
View Article and Find Full Text PDFRedox Biol
September 2025
Department of Cardiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 201620, China. Electronic address:
Pathological cardiac hypertrophy, driven by mitochondrial dysfunction and maladaptive remodeling, remains a therapeutic challenge. This study explores the cardioprotective properties of tectorigenin (Tec) in the context of transverse aortic constriction (TAC)-induced hypertrophy, focusing on mitochondrial homeostasis. In animal models, administration of Tec improved survival rates, reduced cardiac dysfunction, and decreased hypertrophy and fibrosis in TAC mice, while preserving mitochondrial function.
View Article and Find Full Text PDFCell Rep
September 2025
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
Purifying selection that limits the transmission of harmful mitochondrial DNA (mtDNA) mutations has been observed in both human and animal models. Yet, the precise mechanism underlying this process remains undefined. Here, we present a highly specific and efficient in situ imaging method capable of visualizing mtDNA variants that differ by only a few nucleotides at single-molecule resolution in Drosophila ovaries.
View Article and Find Full Text PDFEgypt Heart J
September 2025
Department of Medicine, Faculty of Medicine, Tbilisi State Medical University, Tbilisi, Georgia.
Background: ST-elevation myocardial infarction (STEMI) is a major cardiac event that requires rapid reperfusion therapy. The same reperfusion mechanism that minimizes infarct size and mortality may paradoxically exacerbate further cardiac damage-a condition known as reperfusion injury. Oxidative stress, calcium excess, mitochondrial malfunction, and programmed cell death mechanisms make myocardial dysfunction worse.
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