Autophagy-mediated control of ribosome homeostasis in oncogene-induced senescence

• DOI: 10.1016/j.celrep.2023.113381
• Publication Date: 2023-11-05T09:55:40Z
• Authors: Aida Rodríguez López; Maria H. Jørgensen; Jesper F. Havelund; Frederic S. Arendrup; Srinivasa Prasad ...; Thorbjørn M. Nielsen; Eva Pais; Carsten Jörn Beese; Ahmad Abdul-Al; Anna Constance Vind; Jiri Bartek; Simon Bekker-Jensen; Marta Montes; Panagiotis Galanos; Nils Faergeman; Lotta Happonen; Lisa B. Frankel
• Keywords: Senescence; Ribosomal protein; ribosome biogenesis; Deubiquitinating enzyme

Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent the ribosomal interactome, find deubiquitinase USP10 dissociates from ribosome transition to This release of leads an enhanced ubiquitination, particularly small subunit proteins, including lysine 275 on RPS2. Both reinforcement USP10-ribosome interaction mutation RPS2 K275 abrogate delivery lysosomes without affecting bulk We selective recruitment ubiquitinated autophagosomes mediated p62 receptor. While ribophagy not required establishment per se, it contributes senescence-related metabolome facilitates senescence-associated secretory phenotype.