SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response.
A, Z., H, L., X, S., J, Y., Y, Z., D, S., & A, C. (2026). SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response.. Cardiovascular toxicology. https://doi.org/10.1007/s12012-026-10165-0
A Z, H L, X S, J Y, Y Z, D S, et al. SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response.. Cardiovascular toxicology. 2026; doi: 10.1007/s12012-026-10165-0
A Z, H L, X S, et al. SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response.[J]. Cardiovascular toxicology. 2026. DOI: 10.1007/s12012-026-10165-0.
@article{a2026,
author = {Zeng A and Liu H and Song X and Yan J and Zhou Y and Sun D and Chen A},
title = {SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response.},
journal = {Cardiovascular toxicology},
year = {2026},
doi = {10.1007/s12012-026-10165-0},
note = {PMID: 42489764},
}
TY - JOUR AU - Zeng A AU - Liu H AU - Song X AU - Yan J AU - Zhou Y AU - Sun D AU - Chen A TI - SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response. T2 - Cardiovascular toxicology PY - 2026 DO - 10.1007/s12012-026-10165-0 AN - PMID:42489764 ER -
Doxorubicin (DOX)-induced cardiac injury remains a major limitation of chemotherapy and is closely linked to mitochondrial dysfunction, oxidative stress, and dysregulated mitophagy. Sirtuin 5 (SIRT5), a mitochondrial deacylation-related protein, has been implicated in mitochondrial homeostasis; however, its role in DOX-induced acute cardiaotoxicity is not fully understood. Here, we investigated whether SIRT5 mitigates acute DOX-induced cardiac injury by regulating prohibitin 2 (PHB2) succinylation and mitochondrial quality control. An acute DOX-induced cardiac-damaged mouse model was established (15 mg/kg for one single dose, i.p.) in male C57BL/6 mice, serum lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and cardiac creatine kinase isoenzyme MB (CK-MB) were elevated, accompanied by reduced cardiac SIRT5 expression. In primary cardiomyocytes, DOX (4 µM, 24 h) downregulated SIRT5 and induced excessive ROS production and apoptosis together with altered mitophagy-related signaling. SIRT5 overexpression attenuated DOX-triggered ROS accumulation and apoptosis and reversed these mitophagy-associated alterations. Mechanistically, PHB2 succinylation was increased upon DOX exposure, whereas SIRT5 overexpression reduced PHB2 succinylation detected by PHB2 immunoprecipitation followed by pan-succinyl-lysine immunoblotting. In addition, SIRT5 showed colocalization and interaction with PHB2. Collectively, our findings suggest that SIRT5 attenuates acute DOX-induced cardiotoxicity, potentially through modulating PHB2 succinylation and the mitophagic response, highlighting the SIRT5-PHB2 axis as a candidate target for alleviating early-onset of DOX-induced cardiac injury.