Autophagy最新文献

{"title":"Lactate is a bridge linking glycolysis and autophagy through lactylation.","authors":"Weixia Sun,&nbsp;Mengshu Jia,&nbsp;Yingyan Feng,&nbsp;Xiawei Cheng","doi":"10.1080/15548627.2023.2246356","DOIUrl":"10.1080/15548627.2023.2246356","url":null,"abstract":"<p><p>Lactate is a glycolysis product that is produced from pyruvate by LDH (lactate dehydrogenase) and plays an important role in physiological and pathological processes. However, whether lactate regulates autophagy is still unknown. We recently reported that LDHA is phosphorylated at serine 196 by ULK1 (unc-51 like kinase 1) under nutrient-deprivation conditions, promoting lactate production. Then, lactate mediates PIK3C3/VPS34 lactylation at lysine 356 and lysine 781 via acyltransferase KAT5/TIP60. PIK3C3/VPS34 lactylation enhances the association of PIK3C3/VPS34 with BECN1 (beclin 1, autophagy related), ATG14 and UVRAG, increases PIK3C3/VPS34 lipid kinase activity, promotes macroautophagy/autophagy and facilitates the endolysosomal degradation pathway. PIK3C3/VPS34 hyperlactylation induces autophagy and plays an essential role in skeletal muscle homeostasis and cancer progression. Overall, this study describes an autophagy regulation mechanism and the integration of two highly conserved life processes: glycolysis and autophagy.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3240-3241"},"PeriodicalIF":13.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10019341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AIE-enabled transfection-free identification and isolation of viable cell subpopulations differing in the level of autophagy.","authors":"Wenbin Zhang, Pengfei Wei, Liu Liu, Tao Ding, Yinyin Yang, Peipei Jin, Li Zhang, Zhibin Zhao, Meimei Wang, Bochuan Hu, Xin Jin, Zeng Xu, Han Zhang, Yang Song, Liansheng Wang, Suqin Zhong, Jing Chen, Zhenyu Yang, Ziying Chen, Yu Wu, Zhiming Ye, Youcui Xu, Yunjiao Zhang, Long-Ping Wen","doi":"10.1080/15548627.2023.2235197","DOIUrl":"10.1080/15548627.2023.2235197","url":null,"abstract":"<p><strong>Abbreviations: </strong>3-MA, 3-methyladenine; AIE, aggregation-induced emission; AIEgens, aggregation-induced emission luminogens; ATG5, autophagy related 5; BMDM, bone marrow-derived macrophage; CQ, chloroquine; DiD, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate; DiO, 3,3'-dioctadecyloxacarbocyanine perchlorate; DMSO, dimethyl sulfoxide; d-THP-1, differentiated THP-1; FACS, fluorescence activated cell sorting; FBS, fetal bovine serum; FCCP, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; GABARAP, GABA type A receptor-associated protein; GFP, green fluorescent protein; HBSS, Hanks' balanced salt solution; HPLC, high-performance liquid chromatography; HRP, horseradish peroxidase; IL1B, interleukin 1 beta; KT, an AIE probe composed of a cell-penetrating peptide and an AIEgen tetraphenyl ethylene; LC3-II, lipidated LC3; LDH, lactate dehydrogenase; LIR, LC3-interacting region; LKR, engineered molecular probe composed of an LC3-interacting peptide, a cell-penetrating peptide and a non-AIE fluorescent molecule rhodamine; LKT, engineered molecular probe composed of an LC3-interacting peptide, a cell-penetrating peptide and an AIEgen tetraphenyl ethylene; LPS, lipopolysaccharide; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MEF, mouse embryonic fibroblast; mRFP, monomeric red fluorescent protein; NHS, N-hydroxysuccinimide; NLRP3, NLR family pyrin domain containing 3; PBS, phosphate-buffered saline; PCC, pearson's correlation coefficient; PL, photoluminescence; PMA, phorbol 12-myristate 13-acetate; RAP, rapamycin; RIM, restriction of intramolecular motions; s.e.m., standard error of the mean; SPR, surface plasmon resonance; SQSTM1/p62, sequestosome 1; TAX1BP1, Tax1 binding protein 1; TPE, tetraphenylethylene; TPE-yne, 1-(4-ethynylphenyl)-1,2,2-triphenylethene; Tre, trehalose; u-THP-1: undifferentiated THP-1; UV-Vis, ultraviolet visible.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3062-3078"},"PeriodicalIF":14.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10302420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-based AlphaFold2 significantly expands the structural space of the autophagy pathway.","authors":"Nidhi Malhotra, Shantanu Khatri, Ajit Kumar, Akanksha Arun, Purba Daripa, Saman Fatihi, Sureshkumar Venkadesan, Niyati Jain, Lipi Thukral","doi":"10.1080/15548627.2023.2238578","DOIUrl":"10.1080/15548627.2023.2238578","url":null,"abstract":"<p><strong>Abbreviations: </strong>AF2: AlphaFold2; AF2-Mult: AlphaFold2 multimer; ATG: autophagy-related; CTD: C-terminal domain; ECTD: extreme C-terminal domain; FR: flexible region; MD: molecular dynamics; NTD: N-terminal domain; pLDDT: predicted local distance difference test; UBL: ubiquitin-like.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3201-3220"},"PeriodicalIF":14.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloroplast microautophagy: A green role for NBR1.","authors":"Han Nim Lee, Sarika K Marathe, Marisa S Otegui","doi":"10.1080/15548627.2023.2246857","DOIUrl":"10.1080/15548627.2023.2246857","url":null,"abstract":"","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3244-3245"},"PeriodicalIF":14.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10016616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging Differentially Affects Axonal Autophagosome Formation and Maturation.","authors":"Heather Tsong, Erika Lf Holzbaur, Andrea Kh Stavoe","doi":"10.1080/15548627.2023.2236485","DOIUrl":"10.1080/15548627.2023.2236485","url":null,"abstract":"<p><p>Misregulation of neuronal macroautophagy/autophagy has been implicated in age-related neurodegenerative diseases. We compared autophagosome formation and maturation in primary murine neurons during development and through aging to elucidate how aging affects neuronal autophagy. We observed an age-related decrease in the rate of autophagosome formation leading to a significant decrease in the density of autophagosomes along the axon. Next, we identified a surprising increase in the maturation of autophagic vesicles in neurons from aged mice. While we did not detect notable changes in endolysosomal content in the distal axon during early aging, we did observe a significant loss of acidified vesicles in the distal axon during late aging. Interestingly, we found that autophagic vesicles were transported more efficiently in neurons from adult mice than in neurons from young mice. This efficient transport of autophagic vesicles in both the distal and proximal axon is maintained in neurons during early aging, but is lost during late aging. Our data indicate that early aging does not negatively impact autophagic vesicle transport nor the later stages of autophagy. However, alterations in autophagic vesicle transport efficiency during late aging reveal that aging differentially impacts distinct aspects of neuronal autophagy.<b>Abbreviations:</b> ACAP3: ArfGAP with coiled-coil, ankyrin repeat and PH domains 3; ARF6: ADP-ribosylation factor 6; ATG: autophagy related; AVs: autophagic vesicles; DCTN1/p150^Glued: dynactin 1; DRG: dorsal root ganglia; GAP: GTPase activating protein; GEF: guanine nucleotide exchange factor; LAMP2: lysosomal-associated protein 2; LysoT: LysoTracker; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MAPK8IP1/JIP1: mitogen-activated protein kinase 8 interacting protein 1; MAPK8IP3/JIP3: mitogen-activated protein kinase 8 interacting protein 3; mCh: mCherry; PE: phosphatidylethanolamine.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3079-3095"},"PeriodicalIF":14.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9834271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy is regulated by endoplasmic reticulum calcium homeostasis and sphingolipid metabolism.","authors":"Shiyan Liu, Mutian Chen, Yichang Wang, Huihui Li, Shiqian Qi, Jia Geng, Kefeng Lu","doi":"10.1080/15548627.2023.2249761","DOIUrl":"10.1080/15548627.2023.2249761","url":null,"abstract":"<p><p>Calcium is involved in a variety of cellular processes. As the crucial components of cell membranes, sphingolipids also play important roles as signaling molecules. Intracellular calcium homeostasis, autophagy initiation and sphingolipid synthesis are associated with the endoplasmic reticulum (ER). Recently, through genetic screening and lipidomics analysis in <i>Saccharomyces cerevisiae</i>, we found that the ER calcium channel Csg2 converts sphingolipid metabolism into macroautophagy/autophagy regulation by controlling ER calcium homeostasis. The results showed that Csg2 acts as a calcium channel to mediate ER calcium efflux into the cytoplasm, and deletion of <i>CSG2</i> causes a distinct increase of ER calcium concentration, thereby disrupting the stability of the sphingolipid synthase Aur1, leading to the accumulation of the bioactive sphingolipid phytosphingosine (PHS), which specifically and completely blocks autophagy. In summary, our work links calcium homeostasis, sphingolipid metabolism, and autophagy initiation via the ER calcium channel Csg2.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3256-3257"},"PeriodicalIF":14.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitofissin: a novel mitochondrial fission protein that facilitates mitophagy.","authors":"Tomoyuki Fukuda, Kentaro Furukawa, Tatsuro Maruyama, Nobuo N Noda, Tomotake Kanki","doi":"10.1080/15548627.2023.2237343","DOIUrl":"10.1080/15548627.2023.2237343","url":null,"abstract":"<p><strong>Abbreviations: </strong>Atg: autophagy related; IMM: inner mitochondrial membrane; IMS: intermembrane space; PAS: phagophore assembly site; SAR: selective autophagy receptor.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"3019-3021"},"PeriodicalIF":14.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foot-and-mouth disease virus structural protein VP3 interacts with HDAC8 and promotes its autophagic degradation to facilitate viral replication.","authors":"Huijun Zhang, Xiangwei Wang, Min Qu, Zhiyong Li, Xiangping Yin, Lijie Tang, Xiangtao Liu, Yuefeng Sun","doi":"10.1080/15548627.2023.2233847","DOIUrl":"10.1080/15548627.2023.2233847","url":null,"abstract":"<p><p>Macroautophagy/autophagy has been utilized by many viruses, including foot-and-mouth disease virus (FMDV), to facilitate replication, while the underlying mechanism of the interplay between autophagy and innate immune responses is still elusive. This study showed that HDAC8 (histone deacetylase 8) inhibits FMDV replication by regulating innate immune signal transduction and antiviral response. To counteract the HDAC8 effect, FMDV utilizes autophagy to promote HDAC8 degradation. Further data showed that FMDV structural protein VP3 promotes autophagy during virus infection and interacts with and degrades HDAC8 in an AKT-MTOR-ATG5-dependent autophagy pathway. Our data demonstrated that FMDV evolved a strategy to counteract host antiviral activity by autophagic degradation of a protein that regulates innate immune response during virus infection.<b>Abbreviations</b>: 3-MA: 3-methyladenine; ATG: autophagy related; Baf-A1: bafilomycin A₁; CCL5: C-C motif chemokine ligand 5; Co-IP: co-immunoprecipitation; CQ: chloroquine phosphate; DAPI: 4\",6-diamidino-2-phenylindole; FMDV: foot-and-mouth disease virus; HDAC8: histone deacetylase 8; ISG: IFN-stimulated gene; IRF3: interferon regulatory factor 3; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MAVS: mitochondria antiviral signaling protein; OAS: 2\"-5'-oligoadenylate synthetase; RB1: RB transcriptional corepressor 1; SAHA: suberoylanilide hydroxamic acid; TBK1: TANK binding kinase 1; TCID₅₀: 50% tissue culture infectious doses; TNF/TNF-α: tumor necrosis factor; TSA: trichostatin A; UTR: untranslated region.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"2869-2883"},"PeriodicalIF":14.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9766425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy regulation and protein kinase activity of PIK3C3 controls sertoli cell polarity through its negative regulation on SCIN (scinderin).","authors":"Kehan Wang, Feifei Kong, Yuexin Qiu, Tao Chen, Jiayi Fu, Xin Jin, Youqiang Su, Yayun Gu, Zhibin Hu, Jing Li","doi":"10.1080/15548627.2023.2235195","DOIUrl":"10.1080/15548627.2023.2235195","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Sertoli cells are highly polarized testicular cells that provide a nurturing environment for germ cell development and maturation during spermatogenesis. The class III phosphatidylinositol 3-kinase (PtdIns3K) plays core roles in macroautophagy in various cell types; however, its role in Sertoli cells remains unclear. Here, we generated a mouse line in which the gene encoding the catalytic subunit, &lt;i&gt;Pik3c3&lt;/i&gt;, was specifically deleted in Sertoli cells (cKO) and found that after one round of normal spermatogenesis, the cKO mice quickly became infertile and showed disruption of Sertoli cell polarity and impaired spermiogenesis. Subsequent proteomics and phosphoproteomics analyses enriched the F-actin cytoskeleton network involved in the disorganized Sertoli-cell structure in cKO testis which we identified a significant increase of the F-actin negative regulator SCIN (scinderin) and the reduced phosphorylation of HDAC6, an α-tubulin deacetylase. Our results further demonstrated that the accumulation of SCIN in cKO Sertoli cells caused the disorder and disassembly of the F-actin cytoskeleton, which was related to the failure of SCIN degradation through the autophagy-lysosome pathway. Additionally, we found that the phosphorylation of HDAC6 at site S59 by PIK3C3 was essential for its degradation through the ubiquitin-proteasome pathway. As a result, the HDAC6 that accumulated in cKO Sertoli cells deacetylated SCIN at site K189 and led to a disorganized F-actin cytoskeleton. Taken together, our findings elucidate a new mechanism for PIK3C3 in maintaining the polarity of Sertoli cells, in which both its autophagy regulation or protein kinase activities are required for the stabilization of the actin cytoskeleton.&lt;b&gt;Abbreviations:&lt;/b&gt; ACTB: actin, beta; AR: androgen receptor; ATG14: autophagy related 14; BafA1: bafilomycin A&lt;sub&gt;1&lt;/sub&gt;; BECN1: beclin 1, autophagy related; BTB: blood-testis barrier; CASP3: caspase 3; CDC42: cell division cycle 42; CDH2: cadherin 2; CHX: cycloheximide; CTNNA1: catenin (cadherin associated protein), alpha 1; CYP11A1: cytochrome P450, family 11, subfamily A, polypeptide 1; EBSS: Earle's balanced salt solution; ES: ectoplasmic specialization; FITC: fluorescein isothiocyanate; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCNA: germ cell nuclear acidic protein; GJA1: gap junction protein, alpha 1; H2AX: H2A.X variant histone; HDAC6: histone deacetylase 6; KIT: KIT proto-oncogene, receptor tyrosine kinase; LAMP1: lysosomal associated membrane protein 1; MAP3K5: mitogen-activated protein kinase kinase kinase 5; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; OCLN: occludin; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PNA: arachis hypogaea lectin; RAC1: Rac family small GTPase 1; SCIN: scinderin; SQSTM1/p62: sequestosome 1; SSC: spermatogonia stem cell; STK11: serine/threonine kinase 11; TJP1: tight junction protein 1; TubA: tub","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"2934-2957"},"PeriodicalIF":14.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9781175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPART links autophagy machinery and lipid droplets in motor neurons.","authors":"Shree Padma Metur, Daniel J Klionsky","doi":"10.1080/15548627.2023.2247311","DOIUrl":"10.1080/15548627.2023.2247311","url":null,"abstract":"<p><p>Autophagy, in the form of lipophagy, is an important catabolic pathway mediating the degradation of lipid droplets and mobilization of lipids for physiological function. However, the molecular mechanism and the protein receptors that link lipid droplets/LDs to the autophagy machinery remain unknown. Here, we discuss a recent study by Chung et al. that identifies SPART as the receptor for autophagy of lipid droplets that plays an important role in the turnover of triglycerides in motor neurons.</p>","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"2835-2836"},"PeriodicalIF":14.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10045502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}