ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox

Affiliations

• 1. Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.
• 2. Department of Biochemistry, University of Toronto, Toronto, Canada.
• 3. Biosciences, University of Exeter, Exeter, UK.
• 4. Molecular Medicine Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.
• 5. Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
• 6. Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
• 7. Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Canada.
• 8. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
• 9. College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

PMID: 40638754 DOI: 10.1126/science.adn2804

Abstract

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.

线粒体氧化还原稳态的维持对细胞健康至关重要。线粒体自身拥有一系列内在的抗氧化防御机制，但外界非线粒体抗氧化机制的作用却鲜为人知。我们发现过氧化物酶体可通过接触介导的活性氧（ROS）转移，在维持线粒体氧化还原稳态中发挥直接作用。研究表明，ACBD5和PTPIP51两种蛋白可介导过氧化物酶体与线粒体形成接触位点。在线粒体氧化应激状态下，这类接触位点的占比会增加，且通过将线粒体产生的活性氧转移至过氧化物酶体腔，帮助维持线粒体健康。我们的研究结果揭示了线粒体抗氧化防御的多细胞器层面 —— 提出了过氧化物酶体促进线粒体健康的直接机制 —— 并拓展了已知膜接触位点功能的范围。

Keywords: mitochondrial, ROS, antioxidant，peroxisomes, oxidative stress，ACBD5, PTPIP51

关键词：线粒体，活性氧, 抗氧化，过氧化物酶体, 氧化应激，含酰基辅酶A结合域5, 蛋白酪氨酸磷酸酶相互作用蛋白51，重组蛋白，重组抗体，兔多克隆抗体，佰乐博，佰乐博生物