ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox

• 成果类型: Article
• 署名作者: DiGiovanni, Laura F.; Khroud, Prabhsimran K.; Carmichael, Ruth E.; Schrader, Tina A.; Gill, Shivneet K.; Germain, Kyla; Jomphe, Robert Y.; Wiesinger, Christoph; Boutry, Maxime; Kamoshita, Maki; Snider, Daniel; Stubbings, Garret; Hua, Rong; Garber, Noel; Hacker, Christian; Rutenberg, Andrew D.; Melnyk, Roman A.; Berger, Johannes; Schrader, Michael; Raught, Brian; Kim, Peter K.
• 署名单位: University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Exeter; University of Toronto; Hospital for Sick Children (SickKids); Medical University of Vienna; University of Osaka; Dalhousie University; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; Kyung Hee University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13559
• DOI: 10.1126/science.adn2804
• 发表日期: 2025-07-10
• 页码: 157-162
• 关键词: oxidative stress; beta-oxidation; protein; acbd5; MODEL; maintenance; deficiency; metabolism; software; catalase

摘要

Maintenance of mitochondrial redox homeostasis is of fundamental importance to cellular health. Mitochondria harbor a host of intrinsic antioxidant defenses, but the contribution of extrinsic, nonmitochondrial antioxidant mechanisms is less well understood. We found a direct role for peroxisomes in maintaining mitochondrial redox homeostasis through contact-mediated reactive oxygen species (ROS) transfer. We found that ACBD5 and PTPIP51 form a contact between peroxisomes and mitochondria. The percentage of these contacts increased during mitochondrial oxidative stress and helped to maintain mitochondrial health through the transfer of mitochondrial ROS to the peroxisome lumen. Our findings reveal a multiorganelle layer of mitochondrial antioxidant defense-suggesting a direct mechanism by which peroxisomes contribute to mitochondrial health-and broaden the scope of known membrane contact site functions.