Distinct roles of core autophagy-related genes in zebrafish definitive hematopoiesis
Autophagy. 2023 Nov 3:1-17. doi: 10.1080/15548627.2023.2274251. Online ahead of print.ABSTRACTDespite the well-described discrepancy between ATG (macroautophagy/autophagy-related) genes in the regulation of hematopoiesis, varying essentiality of core ATG proteins in vertebrate definitive hematopoiesis remains largely unclear. Here, we employed zebrafish (Danio rerio) to compare the functions of six core atg genes, including atg13, becn1 (beclin1), atg9a, atg2a, atg5, and atg3, in vertebrate definitive hematopoiesis via clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 ribonucleoprotein and morpholino ...
Source: Autophagy - November 3, 2023 Category: Cytology Authors: Xiang-Ke Chen Zhen-Ni Yi Jack Jark-Yin Lau Alvin Chun-Hang Ma Source Type: research
Distinct roles of core autophagy-related genes in zebrafish definitive hematopoiesis
Autophagy. 2023 Nov 3:1-17. doi: 10.1080/15548627.2023.2274251. Online ahead of print.ABSTRACTDespite the well-described discrepancy between ATG (macroautophagy/autophagy-related) genes in the regulation of hematopoiesis, varying essentiality of core ATG proteins in vertebrate definitive hematopoiesis remains largely unclear. Here, we employed zebrafish (Danio rerio) to compare the functions of six core atg genes, including atg13, becn1 (beclin1), atg9a, atg2a, atg5, and atg3, in vertebrate definitive hematopoiesis via clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 ribonucleoprotein and morpholino ...
Source: Autophagy - November 3, 2023 Category: Cytology Authors: Xiang-Ke Chen Zhen-Ni Yi Jack Jark-Yin Lau Alvin Chun-Hang Ma Source Type: research
Distinct roles of core autophagy-related genes in zebrafish definitive hematopoiesis
Autophagy. 2023 Nov 3:1-17. doi: 10.1080/15548627.2023.2274251. Online ahead of print.ABSTRACTDespite the well-described discrepancy between ATG (macroautophagy/autophagy-related) genes in the regulation of hematopoiesis, varying essentiality of core ATG proteins in vertebrate definitive hematopoiesis remains largely unclear. Here, we employed zebrafish (Danio rerio) to compare the functions of six core atg genes, including atg13, becn1 (beclin1), atg9a, atg2a, atg5, and atg3, in vertebrate definitive hematopoiesis via clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 ribonucleoprotein and morpholino ...
Source: Autophagy - November 3, 2023 Category: Cytology Authors: Xiang-Ke Chen Zhen-Ni Yi Jack Jark-Yin Lau Alvin Chun-Hang Ma Source Type: research
Targeted degradation of SNCA/ α-synuclein aggregates in neurodegeneration using the AUTOTAC chemical platform
In this study, we employed AUTOTAC to synthesize ATC161, a chimeric compound that adopts Anle138b as target-binding ligand (TBL) for SNCA aggregates. The autophagy-targeting ligand (ATL) of ATC161 was designed to allosterically activate the autophagy receptor SQSTSM1/p62 (sequestosome 1), a key step for targeting SNCA aggregates to the phagophore. The lysosomal degradation of SNCA aggregates by ATC161 acutely occurs at DC50 of 100-500 nM with no significant off-target degradation of monomeric SNCA. ATC161 protects cells from DNA and mitochondrial damage by SNCA aggregates. In PD model mice, oral administration of ATC161 de...
Source: Autophagy - November 2, 2023 Category: Cytology Authors: Jihoon Lee Dabin Yoon Ki Woon Sung Eun-Jin Bae Da-Ha Park Young Ho Suh Yong Tae Kwon Source Type: research
Control of ATG14 solubility and autophagy by MARCHF7/MARCH7-mediated ubiquitination
Autophagy. 2023 Nov 1. doi: 10.1080/15548627.2023.2278414. Online ahead of print.ABSTRACTEmerging research has unequivocally demonstrated the significance of post-translational modifications (PTMs) of proteins in orchestrating macroautophagy/autophagy regulation. Ubiquitination is a common PTM of proteins that regulates their stability, activity, and localization, thus playing a crucial role in various cellular processes, including autophagy. In recent work, a ubiquitination-related study revealed that MARCHF7/MARCH7 promotes the mixed polyubiquitination of ATG14 at multiple sites, mainly through the linkages of K6, K11, a...
Source: Autophagy - November 2, 2023 Category: Cytology Authors: Xue Shi Xiaofei Zhang Source Type: research
ATG5 (autophagy related 5) in microglia controls hippocampal neurogenesis in Alzheimer disease
Autophagy. 2023 Nov 1. doi: 10.1080/15548627.2023.2277634. Online ahead of print.ABSTRACTMacroautophagy/autophagy is the intracellular degradation process of cytoplasmic content and damaged organelles. Autophagy is strongly associated with the progression of Alzheimer disease (AD). Microglia are brain-resident macrophages, and recent studies indicate that autophagy in microglia protects neurons from neurodegeneration. Postnatal neurogenesis, the generation of new neurons from adult neural stem cells (NSCs), is impaired in AD patients as well as in AD animal models. However, the extent to which microglial autophagy influenc...
Source: Autophagy - November 2, 2023 Category: Cytology Authors: Xin Tang Ellen Walter Eric Wohleb Yanbo Fan Chenran Wang Source Type: research
Targeted degradation of SNCA/ α-synuclein aggregates in neurodegeneration using the AUTOTAC chemical platform
In this study, we employed AUTOTAC to synthesize ATC161, a chimeric compound that adopts Anle138b as target-binding ligand (TBL) for SNCA aggregates. The autophagy-targeting ligand (ATL) of ATC161 was designed to allosterically activate the autophagy receptor SQSTSM1/p62 (sequestosome 1), a key step for targeting SNCA aggregates to the phagophore. The lysosomal degradation of SNCA aggregates by ATC161 acutely occurs at DC50 of 100-500 nM with no significant off-target degradation of monomeric SNCA. ATC161 protects cells from DNA and mitochondrial damage by SNCA aggregates. In PD model mice, oral administration of ATC161 de...
Source: Autophagy - November 2, 2023 Category: Cytology Authors: Jihoon Lee Dabin Yoon Ki Woon Sung Eun-Jin Bae Da-Ha Park Young Ho Suh Yong Tae Kwon Source Type: research
Control of ATG14 solubility and autophagy by MARCHF7/MARCH7-mediated ubiquitination
Autophagy. 2023 Nov 1. doi: 10.1080/15548627.2023.2278414. Online ahead of print.ABSTRACTEmerging research has unequivocally demonstrated the significance of post-translational modifications (PTMs) of proteins in orchestrating macroautophagy/autophagy regulation. Ubiquitination is a common PTM of proteins that regulates their stability, activity, and localization, thus playing a crucial role in various cellular processes, including autophagy. In recent work, a ubiquitination-related study revealed that MARCHF7/MARCH7 promotes the mixed polyubiquitination of ATG14 at multiple sites, mainly through the linkages of K6, K11, a...
Source: Autophagy - November 2, 2023 Category: Cytology Authors: Xue Shi Xiaofei Zhang Source Type: research
ATG5 (autophagy related 5) in microglia controls hippocampal neurogenesis in Alzheimer disease
Autophagy. 2023 Nov 1. doi: 10.1080/15548627.2023.2277634. Online ahead of print.ABSTRACTMacroautophagy/autophagy is the intracellular degradation process of cytoplasmic content and damaged organelles. Autophagy is strongly associated with the progression of Alzheimer disease (AD). Microglia are brain-resident macrophages, and recent studies indicate that autophagy in microglia protects neurons from neurodegeneration. Postnatal neurogenesis, the generation of new neurons from adult neural stem cells (NSCs), is impaired in AD patients as well as in AD animal models. However, the extent to which microglial autophagy influenc...
Source: Autophagy - November 2, 2023 Category: Cytology Authors: Xin Tang Ellen Walter Eric Wohleb Yanbo Fan Chenran Wang Source Type: research
Automated quantification of vacuole fusion and lipophagy in < em > Saccharomyces cerevisiae < /em > from fluorescence and cryo-soft X-ray microscopy data using deep learning
Autophagy. 2023 Oct 31:1-21. doi: 10.1080/15548627.2023.2270378. Online ahead of print.ABSTRACTDuring starvation in the yeast Saccharomyces cerevisiae vacuolar vesicles fuse and lipid droplets (LDs) can become internalized into the vacuole in an autophagic process named lipophagy. There is a lack of tools to quantitatively assess starvation-induced vacuole fusion and lipophagy in intact cells with high resolution and throughput. Here, we combine soft X-ray tomography (SXT) with fluorescence microscopy and use a deep-learning computational approach to visualize and quantify these processes in yeast. We focus on yeast homolo...
Source: Autophagy - November 1, 2023 Category: Cytology Authors: Jacob Marcus Egebjerg Maria Szomek Katja Thaysen Alice Dupont Juhl Suzana Kozakijevic Stephan Werner Christoph Pratsch Gerd Schneider Sergey Kapishnikov Axel Ekman Richard R öttger Daniel W üstner Source Type: research
CKLF induces microglial activation via triggering defective mitophagy and mitochondrial dysfunction
This study aimed to elucidate the role of microglial mitophagy in CKLF/CKLF1 (chemokine-like factor 1)-induced microglial activation and neuroinflammation, as well as the underlying molecular mechanisms following CKLF treatment. This study determined that CKLF, an inducible chemokine in the brain, leads to an increase in mitophagy markers, such as DNM1L, PINK1 (PTEN induced putative kinase 1), PRKN, and OPTN, along with a simultaneous increase in autophagosome formation, as evidenced by elevated levels of BECN1 and MAP1LC3B (microtubule-associated protein 1 light chain 3 beta)-II. However, SQSTM1, a substrate of autophagy,...
Source: Autophagy - November 1, 2023 Category: Cytology Authors: Hongyun Wang Junrui Ye Ye Peng Wenyu Ma Haodong Chen Hongshuo Sun Zhongping Feng Wenbin He Gang Li Shifeng Chu Zhao Zhang Naihong Chen Source Type: research
SMURF1 controls the PPP3/calcineurin complex and TFEB at a regulatory node for lysosomal biogenesis
This study aimed to show that autophagy regulator SMURF1 controlled TFEB nuclear import for transcriptional activation of the lysosomal biogenesis. We showed that blocking SMURF1 affected lysosomal biogenesis in response to lysosomal damage by preventing TFEB nuclear translocation. It revealed galectins recognized endolysosomal damage, and led to recruitment of SMURF1 and the PPP3/calcineurin apparatus on lysosomes. SMURF1 interacts with both LGALS3 and PPP3CB to form the LGALS3-SMURF1-PPP3/calcineurin complex. Importantly, this complex further stabilizes TFEB, thereby activating TFEB for lysosomal biogenesis. We determine...
Source: Autophagy - November 1, 2023 Category: Cytology Authors: Qin Xia Hanfei Zheng Yang Li Wanting Xu Chengwei Wu Jiachen Xu Shanhu Li Lingqiang Zhang Lei Dong Source Type: research
Automated quantification of vacuole fusion and lipophagy in < em > Saccharomyces cerevisiae < /em > from fluorescence and cryo-soft X-ray microscopy data using deep learning
Autophagy. 2023 Oct 31:1-21. doi: 10.1080/15548627.2023.2270378. Online ahead of print.ABSTRACTDuring starvation in the yeast Saccharomyces cerevisiae vacuolar vesicles fuse and lipid droplets (LDs) can become internalized into the vacuole in an autophagic process named lipophagy. There is a lack of tools to quantitatively assess starvation-induced vacuole fusion and lipophagy in intact cells with high resolution and throughput. Here, we combine soft X-ray tomography (SXT) with fluorescence microscopy and use a deep-learning computational approach to visualize and quantify these processes in yeast. We focus on yeast homolo...
Source: Autophagy - November 1, 2023 Category: Cytology Authors: Jacob Marcus Egebjerg Maria Szomek Katja Thaysen Alice Dupont Juhl Suzana Kozakijevic Stephan Werner Christoph Pratsch Gerd Schneider Sergey Kapishnikov Axel Ekman Richard R öttger Daniel W üstner Source Type: research
CKLF induces microglial activation via triggering defective mitophagy and mitochondrial dysfunction
This study aimed to elucidate the role of microglial mitophagy in CKLF/CKLF1 (chemokine-like factor 1)-induced microglial activation and neuroinflammation, as well as the underlying molecular mechanisms following CKLF treatment. This study determined that CKLF, an inducible chemokine in the brain, leads to an increase in mitophagy markers, such as DNM1L, PINK1 (PTEN induced putative kinase 1), PRKN, and OPTN, along with a simultaneous increase in autophagosome formation, as evidenced by elevated levels of BECN1 and MAP1LC3B (microtubule-associated protein 1 light chain 3 beta)-II. However, SQSTM1, a substrate of autophagy,...
Source: Autophagy - November 1, 2023 Category: Cytology Authors: Hongyun Wang Junrui Ye Ye Peng Wenyu Ma Haodong Chen Hongshuo Sun Zhongping Feng Wenbin He Gang Li Shifeng Chu Zhao Zhang Naihong Chen Source Type: research
SMURF1 controls the PPP3/calcineurin complex and TFEB at a regulatory node for lysosomal biogenesis
This study aimed to show that autophagy regulator SMURF1 controlled TFEB nuclear import for transcriptional activation of the lysosomal biogenesis. We showed that blocking SMURF1 affected lysosomal biogenesis in response to lysosomal damage by preventing TFEB nuclear translocation. It revealed galectins recognized endolysosomal damage, and led to recruitment of SMURF1 and the PPP3/calcineurin apparatus on lysosomes. SMURF1 interacts with both LGALS3 and PPP3CB to form the LGALS3-SMURF1-PPP3/calcineurin complex. Importantly, this complex further stabilizes TFEB, thereby activating TFEB for lysosomal biogenesis. We determine...
Source: Autophagy - November 1, 2023 Category: Cytology Authors: Qin Xia Hanfei Zheng Yang Li Wanting Xu Chengwei Wu Jiachen Xu Shanhu Li Lingqiang Zhang Lei Dong Source Type: research
