{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:04:52Z","timestamp":1784613892990,"version":"3.55.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>ATP5A1 acts as a crucial gene that encodes the core \u03b1 subunit of the mitochondrial F1-ATPase complex to regulate cellular oxidative phosphorylation (OXPHOS) and maintain energy homeostasis. Consequently, its dysregulation\u2014whether through aberrant expression, genomic alterations, or aberrant post-translational modifications\u2014is hypothesized to be a key potential molecular event contributing to the pathogenesis of malignant tumors, neurodegenerative lesions, and metabolic dysregulation.This review systematically summarizes the molecular structure, biological functions, and regulatory networks of ATP5A1. A comprehensive overview of its expression patterns and pathogenic mechanisms across various diseases, including lung, colorectal, liver, and gastric cancers, as well as non-neoplastic conditions, is provided. Besides, emphasis is placed on the clinical translational potential of ATP5A1 as a diagnostic biomarker and therapeutic target, with recent advances in this area critically evaluated. Furthermore, current challenges and limitations in ATP5A1-related research are discussed, and future directions are proposed to facilitate mechanistic investigations and clinical applications. Collectively, this review establishes a comprehensive theoretical framework for understanding the role of ATP5A1 in disease pathogenesis and supports its potential utility in precision diagnostics and therapeutics.<\/jats:p>","DOI":"10.3389\/fcell.2026.1862366","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:34:41Z","timestamp":1784612081000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biological characteristics of ATP5A1 and its pathogenic mechanisms in human diseases: advances in clinical translation"],"prefix":"10.3389","volume":"14","author":[{"given":"Shu-Yin","family":"Yuan","sequence":"first","affiliation":[{"name":"Digestive Disease Center, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Deng","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Juan","family":"Gao","sequence":"additional","affiliation":[{"name":"Emergency Department, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Tang","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Bing","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Hospital Sichuan University Jintang Hospital (Jintang First People\u2019s Hospital)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/370621a0","article-title":"Structure at 2.8 A resolution of F1-ATPase from bovine heart mitochondria","volume":"370","author":"Abrahams","year":"1994","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3390\/biom14030281","article-title":"Mitochondrial dysfunction in advanced maternal aged cumulus cells: a possible link to ATP synthase impairment?","volume":"14","author":"Almeida-Reis","year":"2024","journal-title":"Biomolecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1038\/nature03434","article-title":"Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death","volume":"434","author":"Baines","year":"2005","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1101\/gr.6089707","article-title":"The modifier of min 2 (Mom2) locus: embryonic lethality of a mutation in the Atp5a1 gene suggests a novel mechanism of polyp suppression","volume":"17","author":"Baran","year":"2007","journal-title":"Genome Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1152\/physrev.00001.2015","article-title":"The mitochondrial permeability transition pore: channel formation by F-ATP synthase, integration in signal transduction, and role in pathophysiology","volume":"95","author":"Bernardi","year":"2015","journal-title":"Physiol. 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