{"title":"DJ-1 (PARK7) as a Redox-Responsive Integrator of Pancreatic, Hepatic, and Adipose Crosstalk in Glucose Homeostasis.","authors":"Jayasingha Mudiyanselage Pavithra Sewwandi Jayasingha, Mallika Arachchige Hasantha Madushan, Navodi Sandamini Jayathilaka, Sarvesh Sabarathinam","doi":"10.1002/cph4.70123","DOIUrl":null,"url":null,"abstract":"<p><p>DJ-1 (PARK7), originally characterized in Parkinson's disease, is increasingly recognized as a redox-sensitive regulator of systemic metabolism. Acting through oxidation-dependent modulation of Cys106, DJ-1 integrates cellular redox cues with mitochondrial function, insulin signaling, and stress adaptation pathways. In pancreatic β-cells, it preserves stimulus secretion coupling by stabilizing mitochondrial ATP production. In liver and adipose tissue, DJ-1 maintains insulin responsive signaling and metabolic flexibility through PTEN-PI3K-Akt and antioxidant networks. Loss or over-oxidation of DJ-1 disrupts interorgan glucose coordination, linking chronic redox imbalance to dysglycemia. This review positions DJ-1 as a metabolic sentinel translating oxidative inputs into integrated glucose regulatory outputs.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 2","pages":"e70123"},"PeriodicalIF":6.3000,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comprehensive Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cph4.70123","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
DJ-1 (PARK7), originally characterized in Parkinson's disease, is increasingly recognized as a redox-sensitive regulator of systemic metabolism. Acting through oxidation-dependent modulation of Cys106, DJ-1 integrates cellular redox cues with mitochondrial function, insulin signaling, and stress adaptation pathways. In pancreatic β-cells, it preserves stimulus secretion coupling by stabilizing mitochondrial ATP production. In liver and adipose tissue, DJ-1 maintains insulin responsive signaling and metabolic flexibility through PTEN-PI3K-Akt and antioxidant networks. Loss or over-oxidation of DJ-1 disrupts interorgan glucose coordination, linking chronic redox imbalance to dysglycemia. This review positions DJ-1 as a metabolic sentinel translating oxidative inputs into integrated glucose regulatory outputs.
期刊介绍：
Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered.
This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
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