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Mitophagy, a selective autophagic process critical for mitochondrial quality control, has been linked to various metabolic diseases, but its precise role and the bidirectional interactions with the diabetic bladder microenvironment remain underexplored. This review outlines a novel, self\u2010reinforcing feedback loop central to DBD progression. In this cycle, hyperglycemia impairs both the PINK1\/Parkin\u2010mediated mitophagy pathway and ubiquitin\u2010independent pathways like FUNDC1 under hypoxic conditions, leading to the accumulation of damaged mitochondria. Mitochondrial dysfunction then exacerbates microenvironmental damage through excessive mitochondrial reactive oxygen species (mtROS) production, release of damage\u2010associated molecular patterns (DAMPs), and activation of the NLRP3 inflammasome, which further drives inflammation, fibrosis, and extracellular matrix (ECM) remodeling. This aggravated microenvironment inhibits mitophagy, thereby accelerating the pathogenic cycle. Beyond elucidating this loop, this review suggests that targeting it offers a promising therapeutic strategy. A breakthrough in DBD treatment may necessitate a combined approach that both restores mitophagy and modulates the microenvironment. Additionally, this study critically reviews several promising, yet underexplored, interventions, including pharmacological mitophagy activation with urolithin A, NACHT, LRR, and PYD domains\u2010containing protein 3 (NLRP3) inflammasome inhibition via MCC950, and advanced techniques like nanoparticle\u2010mediated PINK1 mRNA delivery and CRISPR\/Cas9\u2010based Parkin gene editing. Future research should incorporate spatial transcriptomics to resolve cellular heterogeneity, develop targeted nanodelivery systems, and establish mechanism\u2010driven, highly specific combination therapies to enable precision medicine for DBD.<\/jats:p>","DOI":"10.1111\/1753-0407.70199","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:09:23Z","timestamp":1772996963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Interaction Between Mitophagy Dysregulation and the Diabetic Bladder Microenvironment"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2429-1180","authenticated-orcid":false,"given":"Shi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"},{"name":"Department of Urology The Second Clinical Medical College of Nanjing 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