Poster Presentation 11th International Symposium on Autophagy 2025

GABARAP Degradation regulated by Centriolar Satellites is Essential for DNA Damage-Induced Autophagy  (#128)

Yi-Hsuan Lin 1 , Wei-Ting Wang 1 , Chien-Han Kao 1 , Yu-Ching Peng 2 , Won-Jing Wang 1
  1. Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan
  2. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

  DNA damage activates a complex cellular response to maintain genomic integrity and ensure cell survival. Among these responses, autophagy plays a critical role in eliminating damaged organelles, proteins, and nuclear components, thereby limiting genotoxic stress. However, the precise molecular mechanism by which DNA damage triggers autophagy remains poorly defined. In this study, we uncover a novel regulatory pathway in which centrosomal degradation of GABARAP, a member of the Atg8 family, links DNA damage to autophagy activation. Upon genotoxic stress, we observed the disassembly of centriolar satellite granules and degradation of PCM1, a key scaffolding protein of centriolar satellites. This event leads to the targeted degradation of centrosome-localized GABARAP in a manner dependent on the E3 ubiquitin ligase Mib1. Notably, loss of GABARAP at the centrosome strongly enhances LC3B lipidation and promotes autophagy activation, suggesting that centrosomal GABARAP degradation serves as a licensing step for autophagic flux under DNA damage conditions. Our findings define a previously unrecognized centrosome-autophagy signaling axis and highlight GABARAP as a critical mediator of the autophagic response to genotoxic stress.