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ROS-mediated cytoplasmic localization of CARM1 induces mitochondrial fission through DRP1 methylation

Yena Cho1, Yong Kee Kim1

  • 1Muscle Physiome Research Center and Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, 04310, Republic of Korea; College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.

Redox Biology
|June 5, 2024
PubMed

Insights

Coactivator-associated arginine methyltransferase 1 (CARM1) drives cellular senescence by promoting mitochondrial fragmentation and reactive oxygen species (ROS) production. This discovery reveals a key mechanism in the aging process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial dynamics, regulated by fission and fusion, are crucial for cellular health.
  • Cellular senescence is a complex process implicated in aging and disease.

Purpose of the Study:

  • To investigate the role of coactivator-associated arginine methyltransferase 1 (CARM1) in mitochondrial dynamics.
  • To elucidate the molecular mechanisms linking CARM1, mitochondrial function, and cellular senescence.

Main Methods:

  • Investigated CARM1's interaction with dynamin-related protein 1 (DRP1).
  • Analyzed the impact of CARM1-mediated DRP1 methylation on mitochondrial fission.
  • Assessed the role of reactive oxygen species (ROS) in the CARM1-DRP1 pathway and senescence.

Main Results:

  • CARM1 methylates DRP1 at specific residues (R403, R634), promoting mitochondrial fission.
  • Methylated DRP1 interacts with Mff, leading to increased ROS production and mitochondrial fragmentation.
  • A feedback loop involving CARM1 translocation, enhanced DRP1 methylation, and ROS accumulation drives cellular senescence.
  • Depletion of CARM1 or DRP1 inhibits senescence by reducing ROS.

Conclusions:

  • CARM1 plays a critical role in regulating mitochondrial dynamics and inducing cellular senescence.
  • The CARM1-DRP1-ROS axis represents a novel mechanism contributing to the vicious cycle of ROS-induced senescence.
  • This finding provides new insights into the molecular underpinnings of the aging process.
Keywords:
CARM1DRP1MethylationMitochondrial dynamicsROSSenescence

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