Rapamycin Alleviates Heart Failure Caused by Mitochondrial Dysfunction and SERCA Hypoactivity in Syntaxin 12/13 Deficient Models
Source abstract
Abstract
Abstract SYNTAXIN 12/13 (STX12), a member of the syntaxin protein family enriched in the brain and heart, plays important roles in vesicle recycling. Currently, the role of STX12 in cardiovascular physiology remains unclear. Using zebrafish and mice, it is shown that STX12 loss leads to pericardial edema, cardiac malformations, and heart failure. Stx12 depletion disrupts mitochondrial morphology, reduces iron and zinc levels, and impairs ATP production. Stx12‐deficient cardiomyocytes exhibit prolonged repolarization due to decreased sarcoplasmic reticulum Ca2+‐ATPase (SERCA) activity. Treatment with rapamycin, an mTOR inhibitor, restores mitochondrial protein expression and function by prompting the TFEB‐PGC1α axis, enhances SERCA activity via the CAMKII‐phospholamban pathway, and reduces the expression of stress markers. These findings suggest that STX12 plays an important role in the energy metabolism and metal homeostasis of cardiomyocytes. Enhancing mitochondrial function, autophagy, and SERCA activity through the administration of rapamycin may provide a potential therapeutic approach for cardiomyopathies associated with STX12 deficiency and hypometabolism.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Cellular transport and secretion · Ion channel regulation and function · Mitochondrial Function and Pathology
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Clinical Systems Biology Laboratories The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China
Department of Anesthesiology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200000 China
Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology School of Basic Medical Sciences Tianjin Medical University Tianjin 300070 China
Department of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China
Replatium Inc. 55 YuanZhong Road, PuDong New Area Shanghai 201300 China
School of Life Sciences and Technology Tongji University Shanghai 200092 China
Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Shanghai 200031 China
Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Shanghai 200031 China
Funding
National Natural Science Foundation of China
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