| Rapamycin Alleviates Heart Failure Caused by Mitochondrial Dysfunction and SERCA Hypoactivity in Syntaxin 12/13 Deficient Models |
| 論文作者 |
Yang, RZ; Li, F; Liu, J; Li, SA; Liu, DH; Wu, ZB; Liu, PP; Liu, WJ; Zhou, B; Jiang, CZ; Zhang, HB; Yu, Y; Kang, JS |
| 期刊/會議名稱 |
ADVANCED SCIENCE |
| 論文年度 |
2025 |
| 論文類別 |
|
| 摘要 |
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-PGC1 alpha 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. |
| 卷 |
12 |
| 影響因子 |
14.1 |
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