tetano
Editor, Senior Moderator
Nat Commun
. 2024 Oct 16;15(1):8927.
doi: 10.1038/s41467-024-53100-z. Coronavirus M protein promotes mitophagy over virophagy by recruiting PDPK1 to phosphorylate SQSTM1 at T138
Yahui Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Chunyan Li[SUP] #[/SUP][SUP] 1 [/SUP], Chenchen Zhao[SUP] #[/SUP][SUP] 1 [/SUP], Jiayu Wu[SUP] 1 [/SUP], Ya Zhu[SUP] 1 [/SUP], Fei Wang[SUP] 1 [/SUP], Jiepeng Zhong[SUP] 1 [/SUP], Yan Yan[SUP] 1 [/SUP], Yulan Jin[SUP] 1 [/SUP], Weiren Dong[SUP] 1 [/SUP], Jinyang Chen[SUP] 1 [/SUP], Xianghong Yang[SUP] 3 [/SUP], Jiyong Zhou[SUP] 4 5 [/SUP], Boli Hu[SUP] 6 [/SUP]
Affiliations
Autophagy plays a dual role in coronavirus infection, facilitating the elimination of either proviral components (virophagy) or antiviral factors such as mitochondria (mitophagy), leading to complex mechanisms of immune evasion. Understanding the mechanisms that govern the switch between the autophagic degradation of deleterious or beneficial substrates in coronavirus infection is crucial for developing precise drug targets to treat virus-induced diseases. However, this switch remains largely unknown. Using a dual split-fluorescence assay, we identify PDPK1 as a negative regulator of innate immunity, directing the transition from virophagy to mitophagy through the phosphorylation of SQSTM1 at T138. Remarkably, a PDPK1-targeting peptide inhibits the replication of various RNA viruses by restoring innate immunity through enhanced virophagy and suppressed mitophagy, thereby protecting female mice from lethal infections. These findings underscore the detrimental role of PDPK1 in innate immunity by orchestrating the shift from virophagy to mitophagy, positioning PDPK1 as a promising pharmacological target for effectively combating a broad spectrum of virus infections.
. 2024 Oct 16;15(1):8927.
doi: 10.1038/s41467-024-53100-z. Coronavirus M protein promotes mitophagy over virophagy by recruiting PDPK1 to phosphorylate SQSTM1 at T138
Yahui Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Chunyan Li[SUP] #[/SUP][SUP] 1 [/SUP], Chenchen Zhao[SUP] #[/SUP][SUP] 1 [/SUP], Jiayu Wu[SUP] 1 [/SUP], Ya Zhu[SUP] 1 [/SUP], Fei Wang[SUP] 1 [/SUP], Jiepeng Zhong[SUP] 1 [/SUP], Yan Yan[SUP] 1 [/SUP], Yulan Jin[SUP] 1 [/SUP], Weiren Dong[SUP] 1 [/SUP], Jinyang Chen[SUP] 1 [/SUP], Xianghong Yang[SUP] 3 [/SUP], Jiyong Zhou[SUP] 4 5 [/SUP], Boli Hu[SUP] 6 [/SUP]
Affiliations
- PMID: 39414765
- DOI: 10.1038/s41467-024-53100-z
Autophagy plays a dual role in coronavirus infection, facilitating the elimination of either proviral components (virophagy) or antiviral factors such as mitochondria (mitophagy), leading to complex mechanisms of immune evasion. Understanding the mechanisms that govern the switch between the autophagic degradation of deleterious or beneficial substrates in coronavirus infection is crucial for developing precise drug targets to treat virus-induced diseases. However, this switch remains largely unknown. Using a dual split-fluorescence assay, we identify PDPK1 as a negative regulator of innate immunity, directing the transition from virophagy to mitophagy through the phosphorylation of SQSTM1 at T138. Remarkably, a PDPK1-targeting peptide inhibits the replication of various RNA viruses by restoring innate immunity through enhanced virophagy and suppressed mitophagy, thereby protecting female mice from lethal infections. These findings underscore the detrimental role of PDPK1 in innate immunity by orchestrating the shift from virophagy to mitophagy, positioning PDPK1 as a promising pharmacological target for effectively combating a broad spectrum of virus infections.