Academic Journal
SIRT3-mediated deacetylation of ATP5A1 improves mitochondrial function to attenuate myocardial ischemia-reperfusion injury.
| Title: | SIRT3-mediated deacetylation of ATP5A1 improves mitochondrial function to attenuate myocardial ischemia-reperfusion injury. |
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| Authors: | Chen Y; Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China., Xin G; School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China., Zhang H; Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China., Cui X; Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China., Gao J; Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China., Liu Z; Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China., Guo F; Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China., Guo H; Safety Laboratory, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. Electronic address: g0502g@163.com., Fu J; Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. Electronic address: jianhuaffcn@263.net. |
| Source: | Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2026 Aug 06; Vol. 825, pp. 153990. Date of Electronic Publication: 2026 May 19. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2002- >: San Diego, CA : Elsevier Original Publication: New York, Academic Press. |
| MeSH Terms: | Sirtuin 3*/metabolism , Sirtuin 3*/genetics , Myocardial Reperfusion Injury*/metabolism , Myocardial Reperfusion Injury*/pathology , Myocardial Reperfusion Injury*/genetics , Mitochondrial Proton-Translocating ATPases*/metabolism , Mitochondria, Heart*/metabolism , Mitochondria*/metabolism, Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Animals ; Acetylation ; Mice ; Apoptosis ; Mice, Inbred C57BL ; Male ; Cell Line |
| Abstract: | Mitochondrial dysfunction represents a core pathological feature of myocardial ischemia-reperfusion injury (MIRI). Protein acetylation plays a crucial role in regulating mitochondrial function; however, its precise molecular mechanisms in MIRI remain incompletely elucidated. In this study, we performed bioinformatics analysis to screen for differentially expressed genes (DEGs) in MIRI-related datasets (GSE83472, GSE58486, and GSE61592). By integrating these DEGs with mitochondrial gene sets, sirtuin 3 (SIRT3) was identified as a core regulatory molecule. Subsequently, we used SIRT3 inhibitors or plasmid transfection to downregulate or overexpress SIRT3 in MIRI mice and H/R-injured HL-1 cardiomyocytes. The effects of SIRT3 on mitochondrial function and its mediated deacetylation of ATP synthase F1 complex subunit alpha (ATP5A1) on MIRI were evaluated through biochemical assays, histopathology, electron microscopy, immunoprecipitation, and point mutation analysis. Our results demonstrated that under MIRI conditions, SIRT3 expression was downregulated, leading to increased mitochondrial protein acetylation levels, impaired mitochondrial structure, and elevated cardiomyocyte apoptosis. Furthermore, inhibiting SIRT3 expression exacerbated mitochondrial damage and MIRI. Overexpression of SIRT3 significantly reduced ATP5A1 acetylation, restored mitochondrial membrane potential, decreased reactive oxygen species (ROS) production, enhanced mitochondrial respiration, and inhibited cardiomyocyte apoptosis. In summary, SIRT3 improves mitochondrial function by mediating ATP5A1 deacetylation, thereby alleviating MIRI. This finding reveals a novel molecular mechanism and provides a potential therapeutic target for the treatment of MIRI. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. |
| Contributed Indexing: | Keywords: ATP5A1; Acetylation; Bioinformatics analysis; Mitochondrial function; Myocardial ischemia-reperfusion injury; Silent information regulator 3 |
| Substance Nomenclature: | EC 3.5.1.- (Sirtuin 3) EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases) 0 (Sirt3 protein, mouse) EC 3.6.1.14 (ATP5A1 protein, mouse) |
| Entry Date(s): | Date Created: 20260522 Date Completed: 20260604 Latest Revision: 20260606 |
| Update Code: | 20260606 |
| DOI: | 10.1016/j.bbrc.2026.153990 |
| PMID: | 42172898 |
| Database: | MEDLINE |
| ISSN: | 1090-2104 |
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| DOI: | 10.1016/j.bbrc.2026.153990 |