< 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
CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy
In this study, carm1 skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253). In addition to lower mitophagy and autophagy flux in skeletal muscle, carm1 mKO led to increas...
Source: Autophagy - November 29, 2023 Category: Cytology Authors: Derek W Stouth Tiffany L vanLieshout Andrew I Mikhail Sean Y Ng Rozhin Raziee Brittany A Edgett Goutham Vasam Erin K Webb Kevin S Gilotra Matthew Markou Hannah C Pineda Brianna G Bettencourt-Mora Haleema Noor Zachary Moll Megan E Bittner Brendon J Gurd Ke Source Type: research
CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy
In this study, carm1 skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253). In addition to lower mitophagy and autophagy flux in skeletal muscle, carm1 mKO led to increas...
Source: Autophagy - November 29, 2023 Category: Cytology Authors: Derek W Stouth Tiffany L vanLieshout Andrew I Mikhail Sean Y Ng Rozhin Raziee Brittany A Edgett Goutham Vasam Erin K Webb Kevin S Gilotra Matthew Markou Hannah C Pineda Brianna G Bettencourt-Mora Haleema Noor Zachary Moll Megan E Bittner Brendon J Gurd Ke Source Type: research
Communication between small cytosolic dsDNA and autophagy inhibits CGAS (cyclic GMP-AMP synthase) activation
Autophagy. 2023 Nov 27:1-3. doi: 10.1080/15548627.2023.2285612. Online ahead of print.ABSTRACTThe CGAS (cyclic GMP-AMP synthase)-STING1 (stimulator of interferon response cGAMP interactor 1) pathway is an important innate immune pathway that induces proinflammatory cytokine production following stimulation with dsDNA > 45 bp. We recently identified a class of ~ 20-40 bp small cytosolic dsDNA (scDNA) that blocks CGAS-STING1 activation. In this punctum, we discuss the mechanism underlying the inhibition of CGAS-STING1 activation via scDNA. scDNA binds to CGAS but cannot activate its enzymatic activity. It competes with ds...
Source: Autophagy - November 28, 2023 Category: Cytology Authors: Yu-Wei Luo Hongyu Ji Ai-Long Huang Kai-Fu Tang Source Type: research
Communication between small cytosolic dsDNA and autophagy inhibits CGAS (cyclic GMP-AMP synthase) activation
Autophagy. 2023 Nov 27:1-3. doi: 10.1080/15548627.2023.2285612. Online ahead of print.ABSTRACTThe CGAS (cyclic GMP-AMP synthase)-STING1 (stimulator of interferon response cGAMP interactor 1) pathway is an important innate immune pathway that induces proinflammatory cytokine production following stimulation with dsDNA > 45 bp. We recently identified a class of ~ 20-40 bp small cytosolic dsDNA (scDNA) that blocks CGAS-STING1 activation. In this punctum, we discuss the mechanism underlying the inhibition of CGAS-STING1 activation via scDNA. scDNA binds to CGAS but cannot activate its enzymatic activity. It competes with ds...
Source: Autophagy - November 28, 2023 Category: Cytology Authors: Yu-Wei Luo Hongyu Ji Ai-Long Huang Kai-Fu Tang Source Type: research
TRIM22 facilitates autophagosome-lysosome fusion by mediating the association of GABARAPs and PLEKHM1
Autophagy. 2023 Nov 27. doi: 10.1080/15548627.2023.2287925. Online ahead of print.ABSTRACTTripartite motif (TRIM) proteins are a large family of E3 ubiquitin ligases implicated in antiviral defense systems, tumorigenesis, and protein quality control. TRIM proteins contribute to protein quality control by regulating the ubiquitin-proteasome system, endoplasmic reticulum-associated degradation, and macroautophagy/autophagy. However, the detailed mechanisms through which various TRIM proteins regulate downstream events have not yet been fully elucidated. Herein, we identified a novel function of TRIM22 in the regulation of au...
Source: Autophagy - November 27, 2023 Category: Cytology Authors: Hansol Heo Hyungsun Park Myung Shin Lee Jongyoon Kim Juyeong Kim Soon-Young Jung Sun Kyeon Kim Seongju Lee Jaerak Chang Source Type: research
Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy
Autophagy. 2023 Nov 24. doi: 10.1080/15548627.2023.2287932. Online ahead of print.ABSTRACTLC3 lipidation plays an important role in the regulation of macroautophagy and LC3-associated microautophagy. The E1-like enzyme ATG7 is one of the core components that are directly involved in LC3 lipidation reaction. Here, we provide evidence showing that acetylation of ATG7 tightly controls its enzyme activity to regulate the induction of macroautophagy and LC3-associated microautophagy. Mechanistically, acetylation of ATG7 disrupts its interaction with the E2-like enzyme ATG3, leading to an inhibition of LC3 lipidation in vitro an...
Source: Autophagy - November 24, 2023 Category: Cytology Authors: Yinfeng Xu Chuying Qian Qian Wang Lijiang Song Zhengfu He Wei Liu Wei Wan Source Type: research
Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy
Autophagy. 2023 Nov 24. doi: 10.1080/15548627.2023.2287932. Online ahead of print.ABSTRACTLC3 lipidation plays an important role in the regulation of macroautophagy and LC3-associated microautophagy. The E1-like enzyme ATG7 is one of the core components that are directly involved in LC3 lipidation reaction. Here, we provide evidence showing that acetylation of ATG7 tightly controls its enzyme activity to regulate the induction of macroautophagy and LC3-associated microautophagy. Mechanistically, acetylation of ATG7 disrupts its interaction with the E2-like enzyme ATG3, leading to an inhibition of LC3 lipidation in vitro an...
Source: Autophagy - November 24, 2023 Category: Cytology Authors: Yinfeng Xu Chuying Qian Qian Wang Lijiang Song Zhengfu He Wei Liu Wei Wan Source Type: research
