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In our previous study, we demonstrated that age-related AGE accumulation is associated with mitochondrial dysfunction. However, the direct link between mitochondrial dysfunction and AGE accumulation within the context of AD pathogenesis has not yet been fully explored. It also remains unclear whether mitochondrial stress and mitochondrial reactive oxygen species (ROS) drive the accumulation of AGEs. This study, for the first time, provides evidence of progressive AGE accumulation in the cortical mitochondria of AD mice exhibiting mitochondrial dysfunction and A\u03b2 pathology. AGE levels were significantly correlated with A\u03b2-induced mitochondrial dysfunction, oxidative stress, and amyloid pathology. Notably, mitochondrial stress induced by a mitotoxin significantly increased the accumulation of AGEs in cellular and mitochondrial compartments. Scavenging mitochondrial ROS using the mitochondria-targeted antioxidant reduced AGE accumulation and improved mitochondrial function. Our findings highlight the role of mitochondrial dysfunction in AGE metabolism and provide new insights into the pathogenesis of AD.<\/jats:p>","DOI":"10.1371\/journal.pone.0352355","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:30:36Z","timestamp":1782235836000},"page":"e0352355","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitochondrial oxidative stress promotes the accumulation of advanced glycation end products"],"prefix":"10.1371","volume":"21","author":[{"given":"Firoz","family":"Akhter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav","family":"Samanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre 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