Suppression of USP8 sensitizes cells to ferroptosis via SQSTM1/p62-mediated ferritinophagy

• DOI: 10.1093/procel/pwac004
• Publication Date: 2022-10-14T21:24:42Z
• Authors: Lihong Liu; Birong Zheng; Manhui Luo; Jie Du; Fang Yang; Chuanxin Huang; Zengyi Ma; Chunmei Li; Deyin Guo; Hong Peng
• Keywords: Human genetics

Ferroptosis is a newly discovered form of regulated cell death characterized by increased intracellular iron accumulation and subsequent lipid peroxidation (Dixon et al., 2012).Studies have revealed that ferroptosis plays an important role in multiple physiological pathological processes including degenerative diseases, carcinogenesis, cancer immunotherapy (Hassannia 2019, Wang 2019).As storage protein, ferritin degraded via the selective autophagy-mediated degradation process named "ferritinophagy" to regulate homeostasis (Gao 2016).Targeting genes related been corroborated modulate cellular sensitivity (Alvarez 2017, Protchenko 2021).In consideration demand cells than non-cancer enable growth, are more vulnerable iron-catalyzed ferroptosis, prompting induction can be employed as promising approach therapy (Shen 2014, Torti 2018, Hassannia 2019).Several deubiquitinating enzymes (DUBs) OTUB1 BAP1 reported mediate human cancers (Zhang Liu 2019).Ubiquitin-specific peptidase 8 (USP8) originally identified growth-regulated DUB accumulates upon growth stimulation.Although USP8 depletion suppresses proliferation various induces some lines (Islam 2021), whether direct connection exists between remains unknown.Our previous study found decreases autophagic flux through autophagy receptor SQSTM1/p62 (sequestosome 1), thus negatively controls (Peng 2019).Considering correlation we assume may play regulating ferroptosis.Firstly, knockdown (KD) mouse embryonic fibroblasts (MEFs) were constructed confirmed immunoblotting