{"title":"ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.","authors":"Yu Duan, Ze-Chen Shan, Jiao-Jiao Pang, Yu-Guo Chen","doi":"10.1186/s40779-025-00646-8","DOIUrl":null,"url":null,"abstract":"<p><p>Aldehyde dehydrogenase (ALDH) 2, a mitochondrial enzyme, is the main acetaldehyde dehydrogenase involved in the scavenging of alcohol-derived acetaldehyde and endogenous aldehydes. The ALDH2<sup>rs671</sup> mutation affects 560 million East Asians and is closely related to an increased risk of various human diseases. In addition to its well-known function in detoxifying alcohol-derived acetaldehyde and endogenous aldehydes, ALDH2 is implicated in human health through its regulation of autophagic machinery and multiple cell death pathways (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, and NETosis). This review summarizes the current knowledge of ALDH2 and the regulatory mechanism through which ALDH2 regulates autophagy and cell death. In addition, we outline the potential role of ALDH2 in the regulation of autophagy and cell death during the occurrence and progression of human diseases, aiming to provide a novel theoretical framework for human disease treatment.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"58"},"PeriodicalIF":22.9000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445042/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Military Medical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40779-025-00646-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Aldehyde dehydrogenase (ALDH) 2, a mitochondrial enzyme, is the main acetaldehyde dehydrogenase involved in the scavenging of alcohol-derived acetaldehyde and endogenous aldehydes. The ALDH2rs671 mutation affects 560 million East Asians and is closely related to an increased risk of various human diseases. In addition to its well-known function in detoxifying alcohol-derived acetaldehyde and endogenous aldehydes, ALDH2 is implicated in human health through its regulation of autophagic machinery and multiple cell death pathways (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, and NETosis). This review summarizes the current knowledge of ALDH2 and the regulatory mechanism through which ALDH2 regulates autophagy and cell death. In addition, we outline the potential role of ALDH2 in the regulation of autophagy and cell death during the occurrence and progression of human diseases, aiming to provide a novel theoretical framework for human disease treatment.
期刊介绍：
Military Medical Research is an open-access, peer-reviewed journal that aims to share the most up-to-date evidence and innovative discoveries in a wide range of fields, including basic and clinical sciences, translational research, precision medicine, emerging interdisciplinary subjects, and advanced technologies. Our primary focus is on modern military medicine; however, we also encourage submissions from other related areas. This includes, but is not limited to, basic medical research with the potential for translation into practice, as well as clinical research that could impact medical care both in times of warfare and during peacetime military operations.
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