Senecavirus a induces mitophagy to promote self-replication through direct interaction of 2C protein with K27-linked ubiquitinated TUFM catalyzed by RNF185
Autophagy. 2023 Dec 12. doi: 10.1080/15548627.2023.2293442. Online ahead of print.ABSTRACTSenecavirus A (SVA) is a newly emerging picornavirus associated with swine vesicular lesions and neonatal mortality, threatening the global pig industry. Despite sustained efforts, the molecular mechanisms of SVA pathogenesis have not yet been fully elucidated. Here, we demonstrate for the first time that SVA infection can induce complete mitophagy in host cells, which depends on SVA replication. Mitophagy has been subsequently proven to promote SVA replication in host cells. Genome-wide screening of SVA proteins involved in inducing ...
Source: Autophagy - December 12, 2023 Category: Cytology Authors: Meirong Chen Xin Zhang Fanshu Kong Peng Gao Xinna Ge Lei Zhou Jun Han Xin Guo Yongning Zhang Hanchun Yang Source Type: research
LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway
In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention...
Source: Autophagy - December 7, 2023 Category: Cytology Authors: Fei Qin Baoshan Cai Peng Wang Runyu Cao Yuling Zhang Hongling Wen Yi Zheng Wei Zhao Chengjiang Gao Bingyu Liu Source Type: research
LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway
In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention...
Source: Autophagy - December 7, 2023 Category: Cytology Authors: Fei Qin Baoshan Cai Peng Wang Runyu Cao Yuling Zhang Hongling Wen Yi Zheng Wei Zhao Chengjiang Gao Bingyu Liu Source Type: research
LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway
In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention...
Source: Autophagy - December 7, 2023 Category: Cytology Authors: Fei Qin Baoshan Cai Peng Wang Runyu Cao Yuling Zhang Hongling Wen Yi Zheng Wei Zhao Chengjiang Gao Bingyu Liu Source Type: research
LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway
In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention...
Source: Autophagy - December 7, 2023 Category: Cytology Authors: Fei Qin Baoshan Cai Peng Wang Runyu Cao Yuling Zhang Hongling Wen Yi Zheng Wei Zhao Chengjiang Gao Bingyu Liu Source Type: research
UVRAG: orchestrating the initiation of reticulophagy
Autophagy. 2023 Dec 6. doi: 10.1080/15548627.2023.2291937. Online ahead of print.ABSTRACTReticulophagy is a selective autophagy of the endoplasmic reticulum (ER) mediated by cargo receptors. It plays a crucial role in ER quality control, yet the mechanisms that initiate reticulophagy remain poorly understood. Our study identified the multifunctional protein UVRAG (UV radiation resistance associated gene) as a novel regulator of reticulophagy. UVRAG interacts with sheet and tubular reticulophagy receptors, regulates the oligomerization of receptors and facilitates their interaction with LC3/GABARAP, critical for ER fragment...
Source: Autophagy - December 6, 2023 Category: Cytology Authors: Xuehong Qian Jiajia Sun Yixian Cui Source Type: research
UVRAG: orchestrating the initiation of reticulophagy
Autophagy. 2023 Dec 6. doi: 10.1080/15548627.2023.2291937. Online ahead of print.ABSTRACTReticulophagy is a selective autophagy of the endoplasmic reticulum (ER) mediated by cargo receptors. It plays a crucial role in ER quality control, yet the mechanisms that initiate reticulophagy remain poorly understood. Our study identified the multifunctional protein UVRAG (UV radiation resistance associated gene) as a novel regulator of reticulophagy. UVRAG interacts with sheet and tubular reticulophagy receptors, regulates the oligomerization of receptors and facilitates their interaction with LC3/GABARAP, critical for ER fragment...
Source: Autophagy - December 6, 2023 Category: Cytology Authors: Xuehong Qian Jiajia Sun Yixian Cui Source Type: research
< em > Circ-0000953 < /em > deficiency exacerbates podocyte injury and autophagy disorder by targeting < em > Mir665-3p-Atg4b < /em > in diabetic nephropathy
In conclusion, this study revealed that circ -0,000,953 regulates podocyte autophagy by targeting Mir665-3p-Atg4b in DN. Therefore, circ -0,000,953 is a potential biomarker for prevention and cure of DN.Abbreviation: CCL2/MCP-1: C-C motif chemokine ligand 2; ceRNA: competing endogenous RNA; circRNA: circular RNA; cKI: conditional knockin; cKO: conditional knockout; CRE: creatinine; DM: diabetes mellitus; DN: diabetic nephropathy; ESRD: end-stage renal disease; HG: high glucose; IF: immunofluorescence; MAP1LC3/LC3B: microtubule-associated protein 1 light chain 3 beta; MPC5: mouse podocyte clone 5; MTECs: mouse tubular epith...
Source: Autophagy - December 5, 2023 Category: Cytology Authors: Liu Xueqi Ling Jiang Hanxu Zeng Li Gao Shanshan Guo Chaoyi Chen Xinran Liu Mengya Zhang Lijuan Ma Yuanyuan Li Xiangming Qi Yonggui Wu Source Type: research
< em > Circ-0000953 < /em > deficiency exacerbates podocyte injury and autophagy disorder by targeting < em > Mir665-3p-Atg4b < /em > in diabetic nephropathy
In conclusion, this study revealed that circ -0,000,953 regulates podocyte autophagy by targeting Mir665-3p-Atg4b in DN. Therefore, circ -0,000,953 is a potential biomarker for prevention and cure of DN.Abbreviation: CCL2/MCP-1: C-C motif chemokine ligand 2; ceRNA: competing endogenous RNA; circRNA: circular RNA; cKI: conditional knockin; cKO: conditional knockout; CRE: creatinine; DM: diabetes mellitus; DN: diabetic nephropathy; ESRD: end-stage renal disease; HG: high glucose; IF: immunofluorescence; MAP1LC3/LC3B: microtubule-associated protein 1 light chain 3 beta; MPC5: mouse podocyte clone 5; MTECs: mouse tubular epith...
Source: Autophagy - December 5, 2023 Category: Cytology Authors: Liu Xueqi Ling Jiang Hanxu Zeng Li Gao Shanshan Guo Chaoyi Chen Xinran Liu Mengya Zhang Lijuan Ma Yuanyuan Li Xiangming Qi Yonggui Wu Source Type: research
Basal activity of PINK1 and PRKN in cell models and rodent brain
Autophagy. 2023 Dec 2:1-12. doi: 10.1080/15548627.2023.2286414. Online ahead of print.ABSTRACTThe ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads to early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute to disease later in life. While the pathway has been extensively studied in cell culture upon acute and massive mitochondrial stress, basal levels of activation under endogenous c...
Source: Autophagy - December 2, 2023 Category: Cytology Authors: Jens O Watzlawik Fabienne C Fiesel Gabriella Fiorino Bernardo A Bustillos Zahra Baninameh Briana N Markham Xu Hou Caleb S Hayes Jenny M Bredenberg Nicholas W Kurchaba Dominika Fri čová Joanna Siuda Zbigniew K Wszolek Sachiko Noda Shigeto Sato Nobutaka H Source Type: research
Basal activity of PINK1 and PRKN in cell models and rodent brain
Autophagy. 2023 Dec 2:1-12. doi: 10.1080/15548627.2023.2286414. Online ahead of print.ABSTRACTThe ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads to early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute to disease later in life. While the pathway has been extensively studied in cell culture upon acute and massive mitochondrial stress, basal levels of activation under endogenous c...
Source: Autophagy - December 2, 2023 Category: Cytology Authors: Jens O Watzlawik Fabienne C Fiesel Gabriella Fiorino Bernardo A Bustillos Zahra Baninameh Briana N Markham Xu Hou Caleb S Hayes Jenny M Bredenberg Nicholas W Kurchaba Dominika Fri čová Joanna Siuda Zbigniew K Wszolek Sachiko Noda Shigeto Sato Nobutaka H Source Type: research
Basal activity of PINK1 and PRKN in cell models and rodent brain
Autophagy. 2023 Dec 2:1-12. doi: 10.1080/15548627.2023.2286414. Online ahead of print.ABSTRACTThe ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads to early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute to disease later in life. While the pathway has been extensively studied in cell culture upon acute and massive mitochondrial stress, basal levels of activation under endogenous c...
Source: Autophagy - December 2, 2023 Category: Cytology Authors: Jens O Watzlawik Fabienne C Fiesel Gabriella Fiorino Bernardo A Bustillos Zahra Baninameh Briana N Markham Xu Hou Caleb S Hayes Jenny M Bredenberg Nicholas W Kurchaba Dominika Fri čová Joanna Siuda Zbigniew K Wszolek Sachiko Noda Shigeto Sato Nobutaka H Source Type: research
LYC inhibits the AKT signaling pathway to activate autophagy and ameliorate TGFB-induced renal fibrosis
In this study, we demonstrated the specific mechanism of LYC in activating mitophagy and improving renal fibrosis. The enrichment analysis results of GO and KEGG showed that LYC had high enrichment values with autophagy. In this study, we showed that LYC alleviated aristolochic acid I (AAI)-induced intracellular expression of PINK1, TGFB/TGF-β, p-SMAD2, p-SMAD3, and PRKN/Parkin, recruited expression of MAP1LC3/LC3-II and SQSTM1/p62, decreased mitochondrial membrane potential (MMP), and ameliorated renal fibrosis in mice. When we simultaneously intervened NRK52E cells using bafilomycin A1 (Baf-A1), AAI, and LYC, intracellu...
Source: Autophagy - December 1, 2023 Category: Cytology Authors: Yu Wang Zhenlei Ping Hongxin Gao Zhihui Liu Qingyang Xv Xiaowen Jiang Wenhui Yu Source Type: research
LYC inhibits the AKT signaling pathway to activate autophagy and ameliorate TGFB-induced renal fibrosis
In this study, we demonstrated the specific mechanism of LYC in activating mitophagy and improving renal fibrosis. The enrichment analysis results of GO and KEGG showed that LYC had high enrichment values with autophagy. In this study, we showed that LYC alleviated aristolochic acid I (AAI)-induced intracellular expression of PINK1, TGFB/TGF-β, p-SMAD2, p-SMAD3, and PRKN/Parkin, recruited expression of MAP1LC3/LC3-II and SQSTM1/p62, decreased mitochondrial membrane potential (MMP), and ameliorated renal fibrosis in mice. When we simultaneously intervened NRK52E cells using bafilomycin A1 (Baf-A1), AAI, and LYC, intracellu...
Source: Autophagy - December 1, 2023 Category: Cytology Authors: Yu Wang Zhenlei Ping Hongxin Gao Zhihui Liu Qingyang Xv Xiaowen Jiang Wenhui Yu Source Type: research
What's in an E3: role of highly curved membranes in facilitating LC3-phosphatidylethanolamine conjugation during autophagy
Autophagy. 2023 Nov 30:1-3. doi: 10.1080/15548627.2023.2288527. Online ahead of print.ABSTRACTDuring autophagosome formation, ATG3, an E2-like enzyme, catalyzes the transfer of LC3-family proteins (including Atg8 in yeast and LC3- and GABARAP-subfamily members in more complex eukaryotes) from the covalent conjugated ATG3-LC3 intermediate to PE lipids in targeted membranes. A recent study has shown that the catalytically important regions of human ATG3 (hereafter referred to as ATG3), including residues 262 to 277 and 291 to 300, in cooperation with its N-terminal curvature-sensing amphipathic helix (NAH), directly interact...
Source: Autophagy - November 30, 2023 Category: Cytology Authors: Yansheng Ye Maria C Bewley Hong-Gang Wang Fang Tian John M Flanagan Source Type: research
