ROS-mediated cytoplasmic localization of CARM1 induces mitochondrial fission through DRP1 methylationopen access
- Authors
- Cho, Yena; Kim, Yong Kee
- Issue Date
- Jul-2024
- Publisher
- ELSEVIER
- Keywords
- CARM1; DRP1; Methylation; Mitochondrial dynamics; ROS; Senescence
- Citation
- REDOX BIOLOGY, v.73
- Journal Title
- REDOX BIOLOGY
- Volume
- 73
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/160308
- DOI
- 10.1016/j.redox.2024.103212
- ISSN
- 2213-2317
- Abstract
- The dynamic regulation of mitochondria through fission and fusion is essential for maintaining cellular homeostasis. In this study, we discovered a role of coactivator-associated arginine methyltransferase 1 (CARM1) in mitochondrial dynamics. CARM1 methylates specific residues (R403 and R634) on dynamin-related protein 1 (DRP1). Methylated DRP1 interacts with mitochondrial fission factor (Mff) and forms self-assembly on the outer mitochondrial membrane, thereby triggering fission, reducing oxygen consumption, and increasing reactive oxygen species (ROS) production. This sets in motion a feedback loop that facilitates the translocation of CARM1 from the nucleus to the cytoplasm, enhancing DRP1 methylation and ROS production through mitochondrial fragmentation. Consequently, ROS reinforces the CARM1-DRP1-ROS axis, resulting in cellular senescence. Depletion of CARM1 or DRP1 impedes cellular senescence by reducing ROS accumulation. The uncovering of the above-described mechanism fills a missing piece in the vicious cycle of ROS-induced senescence and contributes to a better understanding of the aging process.
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