Autophagy reports最新文献

{"title":"Targeting autophagy to treat HIV immune dysfunction","authors":"Wenli Mu, Heather Martin, Anjie Zhen","doi":"10.1080/27694127.2023.2254615","DOIUrl":"https://doi.org/10.1080/27694127.2023.2254615","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136023924","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}

{"title":"Discovery of autophagy as a universal mechanism for sex steroid synthesis in human ovary and testis.","authors":"Yashar Esmaeilian, Francesko Hela, Gamze Bildik, Ece İltumur, Sevgi Yusufoglu, Kayhan Yakin, Ozgur Oktem","doi":"10.1080/27694127.2023.2251804","DOIUrl":"10.1080/27694127.2023.2251804","url":null,"abstract":"<p><p>We recently discovered that lipophagy is a key mechanism to provide free cholesterol required for steroid biosynthesis in human ovary and testis. Pharmacological or genetic inhibition of autophagy by silencing of the autophagy-related (<i>ATG</i>) genes <i>BECN1</i> (<i>BECLIN1</i>) and <i>ATG5</i> resulted in a significant reduction in basal and gonadotropin-stimulated estradiol, progesterone (P₄) and testosterone production in the ex-vivo explant tissue and cell culture models for ovary and testis. We also described a new mechanism of action for gonadotropin hormones, i.e., follicle stimulating hormone (FSH) and human chorionic gonadotropin (hCG)/luteinizing hormone (LH), in this process. They augment the production of sex steroid hormones by upregulating the expression of <i>ATG</i> genes, the accelerating autophagic flux and promoting LDs sequestration into autophagosomes and degradation in lysosomes. Furthermore, we detected several molecular aberrations at different steps of lipophagy-dependent P₄ production in the ovary of women with defective luteal function. Our findings might have important clinical implications by opening a new avenue for the understanding and treatment of a wide range of diseases varying from reproductive disorders to sex hormone-producing neoplasms and hormone dependent malignancies, such as carcinomas of breast, endometrium, and prostate. <b>Abbreviations:</b> ACAT, Acyl-coenzyme A-cholesterol-acyl-transferase; AMBRA1, autophagy and beclin 1 regulator 1; ATG, autophagy-related; BECN1, BECLIN1; hCG, human chorionic gonadotropin; E_2, estradiol; FSH, follicle stimulating hormone; GABARAP, GABA type A receptor-associated protein; GCs, luteinized granulosa cells; IVF, <i>in vitro</i> fertilization; LAMP2A, lysosomal associated membrane protein 2A; LDs, lipid droplets; LDLs, low-density lipoproteins; P₄: progesterone; PCOS, polycystic ovary syndrome; SOAT1: Sterol-O-acetyltransferase; MAP1LC3B, microtubule associated protein 1 light chain 3 beta; PLIN3, perilipin 3; STAR, steroidogenic acute regulatory protein; SQSTM1, sequestosome-1.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2251804"},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45238189","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}

{"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}

{"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}

{"title":"Multifaceted role of autophagy in regulating phosphate homeostasis and developmental root plasticity.","authors":"Tzu-Yin Liu, Hui-Fang Lung, Chang-Yi Chiu, Hong-Xuan Chow","doi":"10.1080/27694127.2023.2247736","DOIUrl":"10.1080/27694127.2023.2247736","url":null,"abstract":"<p><p>Macroautophagy/autophagy delivers cytoplasmic constituents to the lysosome/vacuole for degradation and recycling, wherein regulates diverse aspects of cellular homeostasis. However, more is needed to know how autophagy activity is fine-tuned at the organismal level to optimize plant fitness in response to developmental and environmental cues. We recently revealed that both basal autophagy and phosphate (Pi) starvation-induced autophagy are required to maintain Pi homeostasis by modulating the expression of PHOSPHATE TRANSPORTER 1 (PHT1) Pi transporters. While Pi limitation preferentially increases the number of autophagic structures and the autophagic flux in the differential zone of the <i>Arabidopsis</i> primary root, Pi starvation-induction of <i>ATG8f</i> and <i>ATG8h</i> expression contributes to the control of autophagic flux in the Pi-deplete root and may participate in promoting root branching for resources exploration. <b>Abbreviations:</b> ATG: autophagy related; PHT1: PHOSPHATE TRANSPORTER 1; Pi: phosphate.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2247736"},"PeriodicalIF":0.0,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47675211","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}

{"title":"Tweaking Ire1 to Unlock Autophagy in Yeast.","authors":"Eshita Das, Ipsita Roy","doi":"10.1080/27694127.2023.2241124","DOIUrl":"10.1080/27694127.2023.2241124","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2241124"},"PeriodicalIF":0.0,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42813190","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}

{"title":"Discovery of small-molecule inhibitors for the protein-protein interactions involving ATG5.","authors":"Honggang Xiang, Renxiao Wang","doi":"10.1080/27694127.2023.2215617","DOIUrl":"10.1080/27694127.2023.2215617","url":null,"abstract":"<p><p>The autophagy-related 12 (ATG12)-autophagy-related 5 (ATG5)-autophagy-related 16-like 1 (ATG16L1) ternary complex forms a dimer that facilitates the translocation of autophagy-related 8 (ATG8) proteins from autophagy-related 3 (ATG3) to phosphatidylethanolamine (PE). This event is fundamental for cargo sequestration and autophagy progression. Thus, one possible strategy for inhibiting autophagy is to disrupt the critical ATG5-ATG16L1 interaction during this process. So far very few known specific autophagy modulators can block autophagy effectively. We recently discovered a small-molecule compound, T1742, which is able to block the ATG5-ATG16L1 and ATG5-TECAIR interactions <i>in vitro</i> at the low-micromolar range (IC₅₀ = 1~2 μM). Flow cytometry assay and western blot experiments indicated that T1742 can also effectively inhibit autophagy in living cells in a dose-dependent manner. To the best of our knowledge, T1742 represents the first small-molecule autophagy inhibitor that disrupts the protein-protein interactions involving ATG5. Such compounds may serve as a new chemical tool for deciphering the mechanism of autophagy or a potential candidate for therapeutic application.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2215617"},"PeriodicalIF":0.0,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43488811","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}

{"title":"Cargo-interacting regions (CIR) of CCPG1 capture ER luminal cargos for reticulophagy.","authors":"Haruka Chino, Shunsuke Ishii, Noboru Mizushima, Eisuke Itakura","doi":"10.1080/27694127.2023.2213560","DOIUrl":"10.1080/27694127.2023.2213560","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) is an organelle that regulates several vital processes necessary to maintain the health of eukaryotic cells. Protein quality control systems selectively remove abnormal ER luminal proteins to maintain ER function. In addition to the ubiquitin-proteasome pathway, the lysosome-dependent selective type of autophagy, reticulophagy (or ER-phagy), plays a crucial role in ER proteostasis. Despite the identification of several reticulophagy receptors, the mechanisms by which cytoplasmic reticulophagy machinery recognizes luminal cargo remain largely unknown. We reported that the reticulophagy receptor CCPG1 (cell cycle progression 1) contains several cargo-interacting regions (CIRs) in its ER luminal region that can directly recognize ER luminal cargos. Our findings suggest that CCPG1 is a key player in sequestering ER luminal cargo into the autophagosome using CIRs. <b>Abbreviations</b>: CIR: cargo-interacting region; CCPG1: cell cycle progression 1; FIR: FIP200-interacting region; IAPP: islet amyloid polypeptide; LIR: LC3-interacting region.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2213560"},"PeriodicalIF":0.0,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45345919","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}

{"title":"Conserved regulation of autophagosome-lysosome fusion through YKT6 phosphorylation.","authors":"Pablo Sánchez-Martín, Claudine Kraft","doi":"10.1080/27694127.2023.2210946","DOIUrl":"10.1080/27694127.2023.2210946","url":null,"abstract":"<p><p>YKT6 is a SNARE (Soluble N-ethylmaleimide-Sensitive Fusion Protein Attachment Protein Receptor) protein governing membrane fusion events of several cellular organelles. In autophagy, YKT6 is involved in early phagophore formation as well as directly in the fusion process between autophagosomes and the lytic compartment. Recently we showed in yeast, mammalian cells, and nematodes that the function of YKT6 in autophagy can be regulated by phosphorylation. Atg1/ULK1 (Unc-51-like kinase 1)-dependent phosphorylation of YKT6 results in autophagy defects during both early (autophagosome formation) and late (autophagosome-lysosome fusion) steps, ultimately resulting in decreased survival of mammalian cells due to defective stress-induced autophagy. These findings show that not only the function but also the regulation of YKT6 is conserved across species.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2210946"},"PeriodicalIF":0.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45950164","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}

{"title":"Autophagy safeguards conidial environmental persistence in filamentous fungi.","authors":"Jin-Li Ding, Ming-Guang Feng, Sheng-Hua Ying","doi":"10.1080/27694127.2023.2205343","DOIUrl":"10.1080/27694127.2023.2205343","url":null,"abstract":"<p><p>Conidiation mechanism confers filamentous fungus efficient dispersal and survival in natural habitats. However, the mechanisms that regulate conidial lifespan and persistence remain enigmatic. We recently revealed that autophagy functions as a sub-cellular mechanism essential for conidial longevity and vitality after maturation <i>in Beauveria bassiana</i>. Significantly, BbApe4 (<i>B. bassiana</i> aspartyl aminopeptidase) contributes to conidial persistence and recovery from dormancy. There are two isoforms for BbAtg8 (<i>B. bassiana</i> autophagy-related protein 8), BbAtg8-α and BbAtg-β. BbApe4 is translocated into vacuoles via its direct binding to BbAtg8-α (hereafter called BbAtg8), which occurs during conidial germination and hyphal growth. The specific interaction between BbAtg8 and BbApe4 is crucial for vacuolar targeting and functionality of BbApe4 and dependent on the autophagic function of BbAtg8. We named the BbApe4-BbAtg8 pathway as simplified cytoplasm-to-vacuole pathway (sCvt) due to the absence of the autophagy receptors that characterize classic yeast Cvt pathway. These findings demonstrate that autophagy acts as a physiological mechanism for fungal survival in nature and highlight the diversity in autophagy-related pathways for vacuolar targeting of hydrolase between fungi. <b>Abbreviations:</b> Bb: <i>Beauveria bassiana</i>; ATG: autophagy-related gene; AIM: Atg8-family interacting motif; Cvt pathway: cytoplasm-to-vacuole targeting pathway; Ape4: aspartyl aminopeptidase.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2205343"},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43284415","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}