癌基因诱导的衰老（OIS）是一种持续的抗增殖反应，可作为防止恶性转化的屏障。在 OIS 过程中，细胞会经历动态重塑，其中涉及通过自噬改变蛋白质和细胞器稳态。在这里，我们发现核糖体在 OIS 过程中选择性地被自噬降解。通过表征核糖体相互作用组中衰老依赖性改变，我们发现去泛素酶 USP10 在向 OIS 过渡期间从核糖体解离。 USP10 的释放导致核糖体泛素化增强，特别是小亚基蛋白，包括 RPS2 上的赖氨酸 275。 USP10-核糖体相互作用的增强和 RPS2 K275 的突变都会消除核糖体向溶酶体的递送，而不影响大量自噬。我们发现泛素化核糖体选择性募集至自噬体是由 p62 受体介导的。虽然核糖体吞噬本身并不是衰老建立所必需的，但它有助于衰老相关的代谢组改变，并促进衰老相关的分泌表型。版权所有 © 2023 作者。由爱思唯尔公司出版。保留所有权利。

Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent alterations in the ribosomal interactome, we find that the deubiquitinase USP10 dissociates from the ribosome during the transition to OIS. This release of USP10 leads to an enhanced ribosome ubiquitination, particularly of small subunit proteins, including lysine 275 on RPS2. Both reinforcement of the USP10-ribosome interaction and mutation of RPS2 K275 abrogate ribosomal delivery to lysosomes without affecting bulk autophagy. We show that the selective recruitment of ubiquitinated ribosomes to autophagosomes is mediated by the p62 receptor. While ribophagy is not required for the establishment of senescence per se, it contributes to senescence-related metabolome alterations and facilitates the senescence-associated secretory phenotype.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.