Pub Date : 2023-10-16DOI: 10.1080/27694127.2023.2267882
Debasna P Panigrahi, Sujit K Bhutia
MTFP1 (mitochondrial fission process 1), an inner mitochondrial membrane protein, plays a crucial role in mitochondrial fission to maintain mitochondrial morphology. Our study found that MTFP1 contains a LIR (LC3-interacting region) to interact with MAP1LC3B (microtubule-associated protein 1 light chain 3 beta) and serves as a mitophagy receptor to eliminate damaged mitochondria. Interestingly, mutation of MTFP1 LIR motif (MTFP1mLIR) inhibits this interaction, decreasing mitophagy in oral cancer cells. Moreover, knockdown of PRKN (parkin RBR E3 ubiquitin protein ligase) or PINK1 (PTEN-induced kinase 1) abolished mitophagy in MTFP1-overexpressing oral cancer cells. In this setting, we observed that MTFP1mLIR-expressing cells display a decrease in TOMM20 (translocase of outer mitochondrial membrane 20) levels without affecting those of COX4 (cytochrome c oxidase subunit 4). In contrast, loss of PRKN or PINK1 caused inhibition of both TOMM20 and COX4 degradation in MTFP1mLIR-expressing cells exposed to cellular stress, suggesting that PRKN may activate the rupture of outer mitochondrial membrane in MTFP1-overexpressing cells for effective mitophagy. We also observed that MTFP1 is beneficial to oral cancer cell survival exposed to anticancer drugs, such as cisplatin, through mitophagy, since inhibition of MTFP1-dependent mitophagy induced cell death. Thus, targeting MTFP1-associated mitophagy could represent a strategy for oral cancer therapy.
{"title":"MTFP1 is a mitophagy receptor that operates in PINK1/PRKN-dependent mitophagy and promotes oral cancer cell survival","authors":"Debasna P Panigrahi, Sujit K Bhutia","doi":"10.1080/27694127.2023.2267882","DOIUrl":"https://doi.org/10.1080/27694127.2023.2267882","url":null,"abstract":"MTFP1 (mitochondrial fission process 1), an inner mitochondrial membrane protein, plays a crucial role in mitochondrial fission to maintain mitochondrial morphology. Our study found that MTFP1 contains a LIR (LC3-interacting region) to interact with MAP1LC3B (microtubule-associated protein 1 light chain 3 beta) and serves as a mitophagy receptor to eliminate damaged mitochondria. Interestingly, mutation of MTFP1 LIR motif (MTFP1mLIR) inhibits this interaction, decreasing mitophagy in oral cancer cells. Moreover, knockdown of PRKN (parkin RBR E3 ubiquitin protein ligase) or PINK1 (PTEN-induced kinase 1) abolished mitophagy in MTFP1-overexpressing oral cancer cells. In this setting, we observed that MTFP1mLIR-expressing cells display a decrease in TOMM20 (translocase of outer mitochondrial membrane 20) levels without affecting those of COX4 (cytochrome c oxidase subunit 4). In contrast, loss of PRKN or PINK1 caused inhibition of both TOMM20 and COX4 degradation in MTFP1mLIR-expressing cells exposed to cellular stress, suggesting that PRKN may activate the rupture of outer mitochondrial membrane in MTFP1-overexpressing cells for effective mitophagy. We also observed that MTFP1 is beneficial to oral cancer cell survival exposed to anticancer drugs, such as cisplatin, through mitophagy, since inhibition of MTFP1-dependent mitophagy induced cell death. Thus, targeting MTFP1-associated mitophagy could represent a strategy for oral cancer therapy.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"86 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136142802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-02DOI: 10.1080/27694127.2023.2256146
Jessica P. Campos-Blázquez, Catalina Flores-Maldonado, Juan M. Gallardo, José Bonilla-Delgado, Alan A. Pedraza-Ramírez, Octavio López-Méndez, Enoc M. Cortés-Malagón, Rubén G. Contreras
Epithelial cells transport substances through the cellular and paracellular pathways. The last one depends on tight junctions, particularly on claudins, the family of integral membrane proteins responsible for the permeability and selectivity of these junctions. 300 nM ouabain (OUA) induces endocytosis and lysosomal degradation of claudin-2 and -4 in an Src and ERK1/2 kinases-dependent manner. Here we investigate whether OUA-induced lysosomal degradation of claudins implicates autophagy in renal epithelial Madin-Darby canine kidney cells. During autophagy, LC3 protein binds phosphatidylethanolamine and incorporates, together with protein p62, into the phagophore. Subsequently, the autolysosome degrades both LC3 and p62 proteins. OUA’s occupancy of its site in the Na⁺/K⁺ATPase (300 nM, 10 h) increases autophagic flux because of degradation of LC3 and p62 and an increase in the number of autophagosomes, as detected by fluorescent LC3 and p62 puncta and the rise in autolysosomes seen by the GFP-LC3-RFP probe. Finally, OUA increases the colocalisation of claudin-1, -2, or -4 with p62 in these puncta. OUA induces autophagy increasing reactive oxygen species generation that activates AMP-activated protein kinase, phosphorylating ULK1 at S555. The autophagy inducer rapamycin causes a degradation of the studied claudins comparable to the one generated by OUA. Furthermore, the autophagy inhibitor dorsomorphin blocks OUA-induced autophagy and claudin-1, -2, and -4 degradation. These results demonstrated that OUA induces claudin-1, -2, and -4 autophagy through oxidative stress.
{"title":"Ouabain promotes claudin-1, -2, and -4 autophagic degradation through oxidative stress and AMPK activation in MDCK cells","authors":"Jessica P. Campos-Blázquez, Catalina Flores-Maldonado, Juan M. Gallardo, José Bonilla-Delgado, Alan A. Pedraza-Ramírez, Octavio López-Méndez, Enoc M. Cortés-Malagón, Rubén G. Contreras","doi":"10.1080/27694127.2023.2256146","DOIUrl":"https://doi.org/10.1080/27694127.2023.2256146","url":null,"abstract":"Epithelial cells transport substances through the cellular and paracellular pathways. The last one depends on tight junctions, particularly on claudins, the family of integral membrane proteins responsible for the permeability and selectivity of these junctions. 300 nM ouabain (OUA) induces endocytosis and lysosomal degradation of claudin-2 and -4 in an Src and ERK1/2 kinases-dependent manner. Here we investigate whether OUA-induced lysosomal degradation of claudins implicates autophagy in renal epithelial Madin-Darby canine kidney cells. During autophagy, LC3 protein binds phosphatidylethanolamine and incorporates, together with protein p62, into the phagophore. Subsequently, the autolysosome degrades both LC3 and p62 proteins. OUA’s occupancy of its site in the Na⁺/K⁺ATPase (300 nM, 10 h) increases autophagic flux because of degradation of LC3 and p62 and an increase in the number of autophagosomes, as detected by fluorescent LC3 and p62 puncta and the rise in autolysosomes seen by the GFP-LC3-RFP probe. Finally, OUA increases the colocalisation of claudin-1, -2, or -4 with p62 in these puncta. OUA induces autophagy increasing reactive oxygen species generation that activates AMP-activated protein kinase, phosphorylating ULK1 at S555. The autophagy inducer rapamycin causes a degradation of the studied claudins comparable to the one generated by OUA. Furthermore, the autophagy inhibitor dorsomorphin blocks OUA-induced autophagy and claudin-1, -2, and -4 degradation. These results demonstrated that OUA induces claudin-1, -2, and -4 autophagy through oxidative stress.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"97 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135899242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-18DOI: 10.1080/27694127.2023.2254614
Hongyu Li, Xiao Yu
As a member of the inositol polyphosphate-5-phosphatase family, INPP5D (inositol polyphosphate-5-phosphatase D) is an important regulator of immune cell activation. To date, the mechanisms underlying anti-malarial immunity have not been elucidated. We recently identified INPP5D as a negative regulator of IFN-I (type I interferon) signaling by promoting autophagic degradation of IRF3 (interferon regulatory factor 3) during malaria infection. Mechanistically, INPP5D enhances the association between IRF3 and the autophagy receptor CALCOCO2/NDP52 (calcium binding and coiled-coil domain 2), which promotes the K63-linked ubiquitination of IRF3 at K313 and serves as a signal for CALCOCO2-dependent selective macroautophagy (hereafter autophagy). Moreover, INPP5D is downregulated by IFN-I-induced miR-155-5p after Plasmodium yoelii (P. yoelii) nigeriensis N67 infection and plays a role as a feedback loop between IFN-I signaling and autophagy. Thus, our study reveals the key role of INPP5D in mediating the crosstalk between IFN-I response and autophagy during anti-malarial immune responses, and suggests that INPP5D may be a potential therapeutic target to control malaria.
{"title":"INPP5D inhibits anti-malarial immunity by promoting IRF3 degradation through selective autophagy","authors":"Hongyu Li, Xiao Yu","doi":"10.1080/27694127.2023.2254614","DOIUrl":"https://doi.org/10.1080/27694127.2023.2254614","url":null,"abstract":"As a member of the inositol polyphosphate-5-phosphatase family, INPP5D (inositol polyphosphate-5-phosphatase D) is an important regulator of immune cell activation. To date, the mechanisms underlying anti-malarial immunity have not been elucidated. We recently identified INPP5D as a negative regulator of IFN-I (type I interferon) signaling by promoting autophagic degradation of IRF3 (interferon regulatory factor 3) during malaria infection. Mechanistically, INPP5D enhances the association between IRF3 and the autophagy receptor CALCOCO2/NDP52 (calcium binding and coiled-coil domain 2), which promotes the K63-linked ubiquitination of IRF3 at K313 and serves as a signal for CALCOCO2-dependent selective macroautophagy (hereafter autophagy). Moreover, INPP5D is downregulated by IFN-I-induced miR-155-5p after Plasmodium yoelii (P. yoelii) nigeriensis N67 infection and plays a role as a feedback loop between IFN-I signaling and autophagy. Thus, our study reveals the key role of INPP5D in mediating the crosstalk between IFN-I response and autophagy during anti-malarial immune responses, and suggests that INPP5D may be a potential therapeutic target to control malaria.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135203607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ATG9A is an important membrane protein in mammalian macroautophagy. The formation of autophagosomes and phagophores is blocked in atg9a KO cells. However, it remains possible that residual membrane formation activity exists in these cells. These precursor structures that precede phagophores are, if they exist, rare and may be difficult to find. Here, we introduce the modified volume correlative light and electron microscopy (CLEM) method to analyze these structures three-dimensionally. In addition to target proteins, mitochondria were labeled as a landmark for precise correlation of slice images by a confocal fluorescence microscope and a focused ion beam scanning electron microscope. We found phagophores and small membrane vesicles near SQSTM1/p62 aggregates in atg9a KO cells, indicating that phagophores could be formed in atg9a-deficient cells, although they were immature and inefficient. Furthermore, we found that RB1CC1/FIP200-positive structures formed clusters around SQSTM1/p62 with ferritin and TAX1BP1. Taken together, our method contributes to the understanding of undiscovered fine structures.
{"title":"Improved volume CLEM revealed that aberrant phagophores and RB1CC1/FIP200-containing clusters appear surround SQSTM1/p62 aggregates in <i>Atg9a</i>-deficient cells","authors":"Soichiro Kakuta, Junji Yamaguchi, Chigure Suzuki, Isei Tanida, Yasuo Uchiyama","doi":"10.1080/27694127.2023.2256599","DOIUrl":"https://doi.org/10.1080/27694127.2023.2256599","url":null,"abstract":"ATG9A is an important membrane protein in mammalian macroautophagy. The formation of autophagosomes and phagophores is blocked in atg9a KO cells. However, it remains possible that residual membrane formation activity exists in these cells. These precursor structures that precede phagophores are, if they exist, rare and may be difficult to find. Here, we introduce the modified volume correlative light and electron microscopy (CLEM) method to analyze these structures three-dimensionally. In addition to target proteins, mitochondria were labeled as a landmark for precise correlation of slice images by a confocal fluorescence microscope and a focused ion beam scanning electron microscope. We found phagophores and small membrane vesicles near SQSTM1/p62 aggregates in atg9a KO cells, indicating that phagophores could be formed in atg9a-deficient cells, although they were immature and inefficient. Furthermore, we found that RB1CC1/FIP200-positive structures formed clusters around SQSTM1/p62 with ferritin and TAX1BP1. Taken together, our method contributes to the understanding of undiscovered fine structures.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135395744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-30DOI: 10.1080/27694127.2023.2251804
Yashar Esmaeilian, Francesko Hela, G. Bildik, Ece İltumur, Sevgi Yusufoglu, K. Yakın, O. Oktem
{"title":"Discovery of autophagy as a universal mechanism for sex steroid synthesis in human ovary and testis","authors":"Yashar Esmaeilian, Francesko Hela, G. Bildik, Ece İltumur, Sevgi Yusufoglu, K. Yakın, O. Oktem","doi":"10.1080/27694127.2023.2251804","DOIUrl":"https://doi.org/10.1080/27694127.2023.2251804","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45238189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-24DOI: 10.1080/27694127.2023.2242715
Samrah Masud, Jiajun Xie, Bart J.M. Grijmans, Sander van der Kooij, Rui Zhang, Tomasz K. Prajsnar, Annemarie H. Meijer
DRAM1 is an infection inducible autophagy modulator, previously shown to promote autophagic and lysosomal defense responses against the intracellular pathogen Mycobacterium marinum. However, its possible role in other anti-bacterial autophagic mechanisms remains unknown. Recently, LC3-associated phagocytosis (LAP) has emerged as autophagy-related mechanism that targets bacteria directly in phagosomes. Our previous work established LAP as the main autophagic mechanism by which macrophages restrict growth of Salmonella Typhimurium in a systemically infected zebrafish host. We therefore employed this infection model to investigate the possible role of Dram1 in LAP. Morpholino knockdown or CRISPR/Cas9-mediated mutation of Dram1 led to reduced host survival and increased bacterial burden during S. Typhimurium infection. In contrast, overexpression of dram1 by mRNA injection curtailed Salmonella replication and reduced mortality of the infected host. During the early response to infection, GFP-Lc3-Salmonella associations were reduced in dram1 knockdown or mutant embryos, and increased by dram1 overexpression. Since LAP is known to require the activity of the phagosomal NADPH oxidase, we used a Salmonella biosensor strain to detect bacterial exposure to reactive oxygen species (ROS) and found that the ROS response was largely abolished with deficiency of dram1, while it was increased with dram1 overexpression. Corroborating these results in a mammalian model, the LC3 and ROS responses to Salmonella were similarly reduced or increased by knockdown or overexpression of Dram1, respectively, in murine RAW264.7 macrophages. Together, these results demonstrate the host protective role of Dram1/DRAM1 during S. Typhimurium infection and suggest a functional link between Dram1/DRAM1 and the induction of LAP.Abbreviations: ATG8: Autophagy related protein 8; ATG16: Autophagy related protein 16; CFU: colony-forming unit; DRAM1: DNA damage regulated autophagy modulator gene 1; dpf: days post fertilization; GFP: green fluorescent protein; hpi: hours post infection; LAP: LC3 associated phagocytosis; LC3, microtubule-associated protein 1 light chain 3; NADPH: Nicotinamide dinucleotide phosphate; p53: Tumor suppressor protein 53: ROS; reactive oxygen species; S. Typhimurium: Salmonella enterica serovar Typhimurium; TIPTP: 2(tetrahydroindazolyl) phenoxy-N-(thiadiazolyl)propenamide 2; UVRAG: UV radiation resistance associated protein
{"title":"DRAM1 confers resistance to <i>Salmonella</i> infection","authors":"Samrah Masud, Jiajun Xie, Bart J.M. Grijmans, Sander van der Kooij, Rui Zhang, Tomasz K. Prajsnar, Annemarie H. Meijer","doi":"10.1080/27694127.2023.2242715","DOIUrl":"https://doi.org/10.1080/27694127.2023.2242715","url":null,"abstract":"DRAM1 is an infection inducible autophagy modulator, previously shown to promote autophagic and lysosomal defense responses against the intracellular pathogen Mycobacterium marinum. However, its possible role in other anti-bacterial autophagic mechanisms remains unknown. Recently, LC3-associated phagocytosis (LAP) has emerged as autophagy-related mechanism that targets bacteria directly in phagosomes. Our previous work established LAP as the main autophagic mechanism by which macrophages restrict growth of Salmonella Typhimurium in a systemically infected zebrafish host. We therefore employed this infection model to investigate the possible role of Dram1 in LAP. Morpholino knockdown or CRISPR/Cas9-mediated mutation of Dram1 led to reduced host survival and increased bacterial burden during S. Typhimurium infection. In contrast, overexpression of dram1 by mRNA injection curtailed Salmonella replication and reduced mortality of the infected host. During the early response to infection, GFP-Lc3-Salmonella associations were reduced in dram1 knockdown or mutant embryos, and increased by dram1 overexpression. Since LAP is known to require the activity of the phagosomal NADPH oxidase, we used a Salmonella biosensor strain to detect bacterial exposure to reactive oxygen species (ROS) and found that the ROS response was largely abolished with deficiency of dram1, while it was increased with dram1 overexpression. Corroborating these results in a mammalian model, the LC3 and ROS responses to Salmonella were similarly reduced or increased by knockdown or overexpression of Dram1, respectively, in murine RAW264.7 macrophages. Together, these results demonstrate the host protective role of Dram1/DRAM1 during S. Typhimurium infection and suggest a functional link between Dram1/DRAM1 and the induction of LAP.Abbreviations: ATG8: Autophagy related protein 8; ATG16: Autophagy related protein 16; CFU: colony-forming unit; DRAM1: DNA damage regulated autophagy modulator gene 1; dpf: days post fertilization; GFP: green fluorescent protein; hpi: hours post infection; LAP: LC3 associated phagocytosis; LC3, microtubule-associated protein 1 light chain 3; NADPH: Nicotinamide dinucleotide phosphate; p53: Tumor suppressor protein 53: ROS; reactive oxygen species; S. Typhimurium: Salmonella enterica serovar Typhimurium; TIPTP: 2(tetrahydroindazolyl) phenoxy-N-(thiadiazolyl)propenamide 2; UVRAG: UV radiation resistance associated protein","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"95 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135465983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-17DOI: 10.1080/27694127.2023.2247309
Yan Hu, Fulvio Reggiori
Macroautophagy/autophagy is a degradative pathway that plays an important role in maintaining cellular homeostasis in eukaryotes. During autophagy, cisternal compartments called phagophores are generated to sequester intracellular components; these structures mature into autophagosomes, which deliver the cargo into lysosomes/vacuoles for degradation. Numerous autophagy-related (Atg) proteins are part of the core machinery that mediates autophagosome biogenesis. Atg9, a lipid scramblase and the only multispanning transmembrane protein among the core Atg machinery, traffics between cytoplasmic reservoirs and the phagophore assembly site (PAS) to provide membranes, recruit other Atg proteins and rearrange lipids on the phagophore membrane. However, the factors mediating Atg9 trafficking remain to be fully understood. In our recent study, we found that the yeast dynamin-like GTPase Vps1 (vacuolar protein sorting 1) is involved in autophagy and is important for Atg9 transport to the PAS. Moreover, we showed that Vps1 function in autophagy requires its GTPase and oligomerization activities. Interestingly, specific mutations in DNM2 (dynamin 2), one of the human homologs of Vps1 that have been linked with specific human diseases such as microcytic anemia and Charcot-Marie-Tooth, also impairs Atg9 transport to the PAS, suggesting that a defect in autophagy may underlay the pathophysiology of these severe human pathologies.
{"title":"The yeast dynamin-like GTPase Vps1 mediates Atg9 transport to the phagophore assembly site in <i>Saccharomyces cerevisiae</i>.","authors":"Yan Hu, Fulvio Reggiori","doi":"10.1080/27694127.2023.2247309","DOIUrl":"10.1080/27694127.2023.2247309","url":null,"abstract":"<p><p>Macroautophagy/autophagy is a degradative pathway that plays an important role in maintaining cellular homeostasis in eukaryotes. During autophagy, cisternal compartments called phagophores are generated to sequester intracellular components; these structures mature into autophagosomes, which deliver the cargo into lysosomes/vacuoles for degradation. Numerous autophagy-related (Atg) proteins are part of the core machinery that mediates autophagosome biogenesis. Atg9, a lipid scramblase and the only multispanning transmembrane protein among the core Atg machinery, traffics between cytoplasmic reservoirs and the phagophore assembly site (PAS) to provide membranes, recruit other Atg proteins and rearrange lipids on the phagophore membrane. However, the factors mediating Atg9 trafficking remain to be fully understood. In our recent study, we found that the yeast dynamin-like GTPase Vps1 (vacuolar protein sorting 1) is involved in autophagy and is important for Atg9 transport to the PAS. Moreover, we showed that Vps1 function in autophagy requires its GTPase and oligomerization activities. Interestingly, specific mutations in DNM2 (dynamin 2), one of the human homologs of Vps1 that have been linked with specific human diseases such as microcytic anemia and Charcot-Marie-Tooth, also impairs Atg9 transport to the PAS, suggesting that a defect in autophagy may underlay the pathophysiology of these severe human pathologies.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2247309"},"PeriodicalIF":0.0,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49465985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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