Chemical modulation of SQSTM1/p62-mediated xenophagy that targets a broad range of pathogenic bacteria

Lee, Yoon Jee; Kim, Jin‐Kyung; Jung, Chan Hoon; Kim, Young Jae; Jung, Eui Jung; Lee, Sang Ho; Choi, Hyungsub; Son, Yeon Sung; Shim, Sang Mi; Jeon, Soyeon; Choe, Jun Ho; Lee, Sang‐Hee; Whang, Jake; Sohn, Kyung-Ah; Hur, Gang Min; Kim, Hyun Tae; Yeom, Jinki; Jo, Eun-Kyeong; Kwon, Yong Tae

doi:10.1080/15548627.2022.2054240

Cited by 28 publications

(20 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4f), indicating that p62 ligand significantly increases autophagic flux. Consistent with a previous report 35 , the mammalian target of rapamycin (mTOR; a master regulator of several signaling pathways, including autophagy) was not modulated by ATB1021 in macrophages (Supplementary Fig. 4).…”

Section: A P62 Ligand Augments Autophagy In Lps-stimulated Macrophagessupporting

confidence: 91%

“…We previously found that p62 ligands are activators of autophagy and xenophagy 35 . Thus, we first examined whether ATB1021 activates autophagy in the presence or absence of LPS in macrophages.…”

Section: A P62 Ligand Augments Autophagy In Lps-stimulated Macrophagesmentioning

confidence: 98%

“…ATB1021 (YT-6-2: (R)-1-(3,4-bis((4-fluorobenzyl)oxy)phenoxy)-3-((2-hydroxyethyl)amino)-propan-2-ol) was synthesized as previously described 35 . Details of the design and synthesis of YTK-2205 (2-((3,4-diphenethoxybenzyl)amino)ethan-1-ol), as well as its ability to modulate p62 in macroautophagy, are available from the World Intellectual Property Organization (https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019190172).…”

Section: Chemical Synthesis Of P62 Ligandsmentioning

confidence: 99%

“…Production and transduction of mouse p62 lentiviral short hairpin RNA Short hairpin RNA (shRNA) was produced using pLKO.1-based target shRNA plasmids (mp62, TRCN0000238133) from Sigma-Aldrich and the appropriate packing plasmid, as in our previous work 35 . For lentiviral infection, PMs or BMDMs cultured in 48-or 24-well plates were infected with lentiviral vector at a multiplicity of infection of 10 for 36 h and then treated with ATB1021 (10 μM) and LPS (100 ng/mL) for the indicated times.…”

Section: Extracellular Acidification Rate Analysismentioning

confidence: 99%

See 3 more Smart Citations

Chemical mimetics of the N-degron pathway alleviate systemic inflammation by activating mitophagy and immunometabolic remodeling

et al. 2023

Self Cite

View full text Add to dashboard Cite

The Arg/N-degron pathway, which is involved in the degradation of proteins bearing an N-terminal signal peptide, is connected to p62/SQSTM1-mediated autophagy. However, the impact of the molecular link between the N-degron and autophagy pathways is largely unknown in the context of systemic inflammation. Here, we show that chemical mimetics of the N-degron Nt-Arg pathway (p62 ligands) decreased mortality in sepsis and inhibited pathological inflammation by activating mitophagy and immunometabolic remodeling. The p62 ligands alleviated systemic inflammation in a mouse model of lipopolysaccharide (LPS)-induced septic shock and in the cecal ligation and puncture model of sepsis. In macrophages, the p62 ligand attenuated the production of proinflammatory cytokines and chemokines in response to various innate immune stimuli. Mechanistically, the p62 ligand augmented LPS-induced mitophagy and inhibited the production of mitochondrial reactive oxygen species in macrophages. The p62 ligand-mediated anti-inflammatory, antioxidative, and mitophagy-activating effects depended on p62. In parallel, the p62 ligand significantly downregulated the LPS-induced upregulation of aerobic glycolysis and lactate production. Together, our findings demonstrate that p62 ligands play a critical role in the regulation of inflammatory responses by orchestrating mitophagy and immunometabolic remodeling.

show abstract

Section: A P62 Ligand Augments Autophagy In Lps-stimulated Macrophagessupporting

confidence: 91%

Section: A P62 Ligand Augments Autophagy In Lps-stimulated Macrophagesmentioning

confidence: 98%

Section: Chemical Synthesis Of P62 Ligandsmentioning

confidence: 99%

Section: Extracellular Acidification Rate Analysismentioning

confidence: 99%

See 2 more Smart Citations

Chemical mimetics of the N-degron pathway alleviate systemic inflammation by activating mitophagy and immunometabolic remodeling

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Typhimurium (S. Typhimurium), can be enveloped by ubiquitin proteins and recognized by autophagy receptors, such as p62, NDP52, OPTN, and TAX1BP1. With these receptors' help, cytoplasmic bacteria are targeted to autophagosome (Thurston et al, 2009;Tumbarello et al, 2015;Lee et al, 2022). In addition to ubiquitin, galectin-8, a cytosolic lectin, detects S. Typhimurium invasion by binding host glycans after being exposed to damaged Salmonellacontaining vacuole (SCV).…”

Section: Autophagy Plays a Protective Role In Inflammation By Interac...mentioning

confidence: 99%

Interaction Between Autophagy and Porphyromonas gingivalis-Induced Inflammation

Kang

Dai²,

Wang³

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as pathogen microbial infection and body tissue damage. Porphyromonas gingivalis infection elicits both autophagy and inflammation, and dysregulation of autophagy and inflammation promotes pathology. This review focuses on the interaction between autophagy and inflammation caused by Porphyromonas gingivalis infection, aiming to elaborate on the possible mechanism involved in the interaction.

show abstract

Exploring the Function of OPTN From Multiple Dimensions

Guo,

Tian,

Xia

et al. 2024

Cell Biochemistry & Function

View full text Add to dashboard Cite

Autophagy is an essential intracellular degradation system responsible for delivering cytoplasmic components to lysosomes. Within this intricate process, optineurin (OPTN), an autophagy receptor, has attracted extensive attention due to its multifaceted roles in the autophagy process. OPTN is regulated by various posttranslational modifications and actively participates in numerous signaling pathways and cellular processes. By exploring the regulatory mechanism of OPTN posttranslational modification, we can further understand the critical role of protein posttranslational modification in biological progress, such as autophagy. Additionally, OPTN is implicated in many human diseases, including rheumatoid arthritis, osteoporosis, and infectious diseases. And we delve into the inflammatory pathways regulated by OPTN and clarify how it regulates inflammatory diseases and cancer. We aim to enhance the understanding of OPTN's multifaceted functions in cellular processes and its implications in the pathogenesis of inflammatory diseases and cancer.

show abstract

Chemical modulation of SQSTM1/p62-mediated xenophagy that targets a broad range of pathogenic bacteria

Cited by 28 publications

References 95 publications

Chemical mimetics of the N-degron pathway alleviate systemic inflammation by activating mitophagy and immunometabolic remodeling

Chemical mimetics of the N-degron pathway alleviate systemic inflammation by activating mitophagy and immunometabolic remodeling

Interaction Between Autophagy and Porphyromonas gingivalis-Induced Inflammation

Exploring the Function of OPTN From Multiple Dimensions

Contact Info

Product

Resources

About