Autophagy reports最新文献

{"title":"Obesity-related proximal tubulopathy: an emerging threat to kidney health.","authors":"Takeshi Yamamoto, Jun Nakamura, Yoshitsugu Takabatake, Yoshitaka Isaka","doi":"10.1080/27694127.2023.2200341","DOIUrl":"10.1080/27694127.2023.2200341","url":null,"abstract":"<p><p>Our previous studies have demonstrated that lipid overload leads to lysosomal dysfunction and autophagic stagnation in kidney proximal tubular epithelial cells (PTECs), which contributes to the renal lipotoxicity and eventually leading to the development of an obesity-related kidney disease. Here we identified that TFEB (transcription factor EB) is a modulator of PTECs lipotoxicity. Exposure to saturated fatty acid enhanced TFEB dephosphorylation and nuclear translocation in PTECs. In a mouse model fed with a high-fat diet (HFD), activated TFEB counteracted phospholipid accumulation in lysosomes by promoting lysosomal exocytosis in PTECs. Conversely, HFD-fed, PTECs-specific <i>tfeb</i> ^-/- deficient mice exhibited increased phospholipid accumulation and autophagic stagnation, which made kidney vulnerable to injury following ischemia-reperfusion. Moreover, a higher body mass index was correlated to reductions in TFEB nuclear translocation in PTECs of chronic kidney disease patients. These data suggest that PTECs are involved in the pathogenesis of obesity-related kidney disease, which is called obesity-related proximal tubulopathy. <b>Abbreviations:</b> EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; GAP: GTPase activating protein; HFD: high-fat diet; I/R: ischemia-reperfusion; LMP: lysosomal membrane permeabilization; LRP2: low density lipoprotein receptor-related protein 2; MLBs: multilamellar bodies; MTORC1: mechanistic target of rapamycin kinase complex 1; ORT: obesity-related proximal tubulopathy; PA: palmitic acid; PTEC: proximal tubular epithelial cell; RRAG: Ras related GTP binding; RPS6KB1, ribosomal protein S6 kinase B1; TFEB: transcription factor EB.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2200341"},"PeriodicalIF":0.0,"publicationDate":"2023-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49601166","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":"A novel autophagy inhibitor, bTBT, disturbs autophagosome formation.","authors":"Momoka Chiba, Mai Yanagawa, Yurika Oyama, Shingo Harada, Tetsuhiro Nemoto, Akira Matsuura, Eisuke Itakura","doi":"10.1080/27694127.2023.2194620","DOIUrl":"10.1080/27694127.2023.2194620","url":null,"abstract":"<p><p>Macroautophagy (hereafter, autophagy) is a form of intracellular degradation in which autophagosome formation is systematically coordinated by multiple processes involving numerous autophagy-related gene (ATG) proteins. Autophagy-modulating compounds are valuable for understanding the molecular mechanism of autophagy and its clinical application. Although several autophagy inhibitors have been identified, their inhibitory steps during autophagosome formation by the inhibitors are limited. Herein, we identified a novel autophagy inhibitor, bis-tributyltin (bTBT), which inhibits a unique step in autophagosome formation. In mammalian cells, bTBT treatment suppresses LC3 flux and accumulates most of ATG proteins, including LC3 and early ATG proteins (ULK1, ATG16L1, and WIPI2), in punctate structures. On the other hand, LAMP1, a lysosomal marker, did not co-localize with accumulated LC3 after bTBT treatment, indicating bTBT inhibits a late step of autophagosome formation. Stx17, a soluble <i>N</i>-ethylmaleimide-sensitive factor attachment protein receptor protein that mediates autophagosome-lysosome fusion, is usually recruited to LC3-positive structures after the dissociation of early ATG proteins. However, bTBT accumulates Stx17 and WIPI2 positive large autophagic structures and maintains the autophagic structures for much longer. In conclusion, we identified a novel type of autophagy inhibitor, bTBT, which disturbs autophagosome formation.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2194620"},"PeriodicalIF":0.0,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43561749","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":"A crosstalk between phosphorylation and ubiquitination of BNIP3 regulates mitophagy under hypoxia.","authors":"Yun-Ling He, Jian Li, Yan Cao, Hai-Tao Wu, Li-Ying Wu","doi":"10.1080/27694127.2023.2197637","DOIUrl":"10.1080/27694127.2023.2197637","url":null,"abstract":"<p><p>BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3) is a mitochondrial outer membrane protein that is sensitive to hypoxia and mediates mitophagy, a process important for mitochondrial quality control and to maintain energetic and redox homeostasis under hypoxia. It has been reported that up-regulation of BNIP3, which acts as mitophagy receptor, promotes mitophagy. In our recent study, we found that the post-translational modification of BNIP3 is crucial to induce mitophagy, and that a crosstalk between phosphorylation/dephosphorylation and ubiquitination acts as a switch to control BNIP3-mediated mitophagy under hypoxia. We demonstrated that the phosphorylation of BNIP3 at S60 and T66 by MAPK8/9 (mitogen-activated protein kinase 8/9) under hypoxia blocks the degradation of BNIP3 via the ubiquitin-proteasome pathway and enhances its interaction with MAP1LC3 (microtubule associated protein 1 light chain 3), thereby promoting mitophagy. In contrast, dephosphorylation of BNIP3 by members of the PP1/2A (protein phosphatase PP1 and PP2A) phosphatase subfamily under hypoxia accelerates degradation of BNIP3 via the ubiquitin-proteasome pathway, thereby suppressing mitophagy. Altogether, these findings provide knowledge necessary to devise intervention strategies for hypoxia-related diseases and/or hypoxia-related developmental processes. <b>Abbreviations:</b> BCL2: BCL2 apoptosis regulator; BCL2L1: BCL2 like 1; BECN1: beclin 1, autophagy related; BH3: BCL2 homology 3; BNIP3: BCL2/adenovirus e1B 19 kDa protein interacting protein 3; LIR: MAP1LC3-interacting region; MAP1LC3: microtubule associated protein 1 light chain 3; MAPK8: mitogen-activated protein kinase 8; MAPK9: mitogen-activated protein kinase 9; PEST: rich in amino acids P, E, S, T, and D; PP1: protein phosphatase 1; PP2A: protein phosphatase 2A; PEST: rich in amino acids P, E, S, T, and D.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2197637"},"PeriodicalIF":0.0,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47922831","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":"Atg8 family proteins, LIR/AIM motifs and other interaction modes.","authors":"Vladimir V Rogov, Ioannis P Nezis, Panagiotis Tsapras, Hong Zhang, Yasin Dagdas, Nobuo N Noda, Hitoshi Nakatogawa, Martina Wirth, Stephane Mouilleron, David G McEwan, Christian Behrends, Vojo Deretic, Zvulun Elazar, Sharon A Tooze, Ivan Dikic, Trond Lamark, Terje Johansen","doi":"10.1080/27694127.2023.2188523","DOIUrl":"10.1080/27694127.2023.2188523","url":null,"abstract":"<p><p>The Atg8 family of ubiquitin-like proteins play pivotal roles in autophagy and other processes involving vesicle fusion and transport where the lysosome/vacuole is the end station. Nuclear roles of Atg8 proteins are also emerging. Here, we review the structural and functional features of Atg8 family proteins and their protein-protein interaction modes in model organisms such as yeast, <i>Arabidopsis, C. elegans</i> and <i>Drosophila</i> to humans. Although varying in number of homologs, from one in yeast to seven in humans, and more than ten in some plants, there is a strong evolutionary conservation of structural features and interaction modes. The most prominent interaction mode is between the LC3 interacting region (LIR), also called Atg8 interacting motif (AIM), binding to the LIR docking site (LDS) in Atg8 homologs. There are variants of these motifs like \"half-LIRs\" and helical LIRs. We discuss details of the binding modes and how selectivity is achieved as well as the role of multivalent LIR-LDS interactions in selective autophagy. A number of LIR-LDS interactions are known to be regulated by phosphorylation. New methods to predict LIR motifs in proteins have emerged that will aid in discovery and analyses. There are also other interaction surfaces than the LDS becoming known where we presently lack detailed structural information, like the N-terminal arm region and the UIM-docking site (UDS). More interaction modes are likely to be discovered in future studies.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49651386","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":"Survival of intracellular pathogens in response to mTORC1- or TRPML1-TFEB-induced xenophagy.","authors":"Mariana I Capurro, Akriti Prashar, Xiaodong Gao, Nicola L Jones","doi":"10.1080/27694127.2023.2191918","DOIUrl":"10.1080/27694127.2023.2191918","url":null,"abstract":"<p><p>Intracellular pathogens establish persistent infections by generating reservoirs that protect them from the action of antibiotics and the host immune response. Novel therapeutics should then target the host pathways exploited by the pathogens to form these intracellular niches. An attractive strategy to achieve this is inducing xenophagy, the selective autophagy that recognizes and targets invading pathogens for degradation. However, some bacteria have evolved mechanisms to co-opt xenophagy for their own benefit. Therefore, in this study we determine the effect of inducing xenophagy by different pathways, namely the inhibition of MTOR or through TRPML1-TFEB activation, on the fate of pathogens that are either susceptible to, evade or require autophagy for intracellular survival. We identified a dose of rapamycin that exclusively induces autophagy through MTOR inhibition and used ML-SA1 to activate the TRPML1-TFEB pathway, which also increases lysosomal biogenesis. We found that ML-SA1 induced greater autophagy flux than rapamycin. By performing in vitro infections with <i>H. pylori, S</i>. Typhimurium, <i>S. flexneri, L. monocytogenes</i> and <i>S. aureus</i>, we established that ML-SA1 had a more potent effect than rapamycin in restricting the growth of pathogens susceptible to xenophagy. In the case of pathogens that produce effectors to block xenophagy, ML-SA1, but not rapamycin, resulted in bacterial killing. During <i>S. aureus</i> infection, which depends on autophagy for intracellular survival, ML-SA1 administration potentiated bacterial growth. We suggest that while targeting the xenophagy pathway holds promise for treatment of intracellular pathogens, a precision approach to select the correct target to induce effective bacterial killing is warranted. <b>Abbreviations</b>: 3-MA: 3-methyladenine, ATG: autophagy-related protein, Baf: bafilomycin A1; Ca2+: calcium, CFU: colony-forming units, DMSO: dimethyl sulfoxide, h: hour, <i>Hp: Helicobacter pylori</i>, hpi: hours post-infection, Lamp1: lysosomal-associated membrane protein 1, LC3: microtubule-associated protein 1A/1B-light chain, <i>Lm: Listeria monocytogenes</i>, LSD: lysosomal storage disorder, min: minutes, mTOR: mechanistic target of rapamycin; mTORC1: mechanistic target of rapamycin complex 1, MEF: mouse embryonic fibroblast, μM: micromolar, moi: multiplicity of infection, nM: nanomolar, OD: optical density, PBS: phosphate buffer saline, <i>Sa: Staphylococcus aureus</i>, SCV: <i>Salmonella</i> containing vacuole, Sifs: <i>Salmonella</i>-induced filaments, <i>Sf: Shigella flexneri</i>, SLAPs: Spacious Listeria containing phagosomes, <i>St: Salmonella</i> Typhimurium TFEB: transcription factor EB, TRPML1: transient receptor potential membrane channel 1, VacA: vacuolating cytotoxin, wt: wild-type.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2191918"},"PeriodicalIF":0.0,"publicationDate":"2023-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43590026","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":"Does Exercise Regulate Autophagy in Humans? A Systematic Review and Meta-Analysis.","authors":"Xiang-Ke Chen, Chen Zheng, Parco Ming-Fai Siu, Feng-Hua Sun, Stephen Heung-Sang Wong, Alvin Chun-Hang Ma","doi":"10.1080/27694127.2023.2190202","DOIUrl":"10.1080/27694127.2023.2190202","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Macroautophagy/autophagy is an essential recycling process that is involved in a wide range of biological functions as well as in diseases. The regulation of autophagy by exercise and the associated health benefits have been revealed by rodent studies over the past decade, but the evidence from human studies remains inconclusive.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The MEDLINE, Embase, Cochrane, Scopus, and Web of Science databases were systematically searched from inception until September 2022. Human studies that explored potential effects of physical exercise on autophagy at the protein level were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model was used for the meta-analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-six studies were included in the meta-analysis. Subgroup analyses revealed that an acute bout of resistance exercise attenuated autophagy, as characterized by lower levels of microtubule-associated proteins 1A/1B light chain 3B (LC3-II) and higher levels of sequestosome 1 (SQSTM1). In contrast, the long-term resistance exercise elevated autophagy, as shown by higher levels of LC3-II and lower levels of SQSTM1. No significant changes in LC3-II levels were observed with moderate- or vigorous-intensity endurance exercise either as an acute bout or long-term. In terms of tissue types, exercise exerted opposite effects between skeletal muscles and peripheral blood mononuclear cells (PBMCs), whereby autophagy was suppressed in skeletal muscles when activated in the PBMCs. Other meta-analyses have also shown significant alterations in the level of many canonical autophagic and mitophagic proteins, including unc-51 like autophagy activating kinase (ULK1)&lt;sup&gt;S317&lt;/sup&gt;, ULK1&lt;sup&gt;S757&lt;/sup&gt;, Beclin-1, ATG12, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3, and PARKIN following exercise, suggesting the activation of canonical autophagy and mitophagy, although the scope of those analyses was more limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our findings demonstrate that physical exercise probably regulates autophagy in an exercise modality- and tissue-dependent manner in humans, although further investigation is needed. Customized exercise prescriptions should be aimed for when implementing exercise to regulate autophagy in humans.&lt;b&gt;Abbreviations:&lt;/b&gt; ATG: autophagy-related gene; BCL2L13: BCL2-like 13; BECN1: beclin1; BNIP3: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; GABARAP: gamma-aminobutyric acid receptor-associated protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; LAMP2: lysosome-associated membrane protein 2; LC3B: microtubule-associated proteins 1A/1B light chain 3B; MD: mean difference; mTOR: mammalian target of rapamycin; PBMC: peripheral blood mononuclear cells; PINK1: PTEN-induced kinase 1; PRISMA: preferred reporting items for systematic review and meta-analysis; SD: standard deviation; SQSTM1: s","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2190202"},"PeriodicalIF":0.0,"publicationDate":"2023-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43054119","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":"Gamma-aminobutyric acid type A receptor alpha 4 coordinates autophagy, inflammation, and immunometabolism to promote innate immune activation.","authors":"Jin Kyung Kim, Prashanta Silwal, Young Jae Kim, Sang Min Jeon, In Soo Kim, June-Young Lee, Jun Young Heo, Sang-Hee Lee, Jin-Woo Bae, Jin-Man Kim, Jin Bong Park, Eun-Kyeong Jo","doi":"10.1080/27694127.2023.2181915","DOIUrl":"10.1080/27694127.2023.2181915","url":null,"abstract":"<p><p>Gamma-aminobutyric acid type A receptor (GABA_AR), the ionotropic receptor of GABA, is expressed in macrophages and in the nervous system; however, its role in innate immunity is unknown. Herein, we identified myeloid GABA_AR subunit α4 (<i>Gabra4</i>) as a critical regulator of autophagy and a promoter of host innate defense during infection and inflammation. Myeloid <i>Gabra4</i> deficiency led to defective mycobacterial clearance during infection and increased susceptibility to septic shock. <i>Gabra4</i> deletion exaggerated inflammatory responses and suppressed the activation of autophagy in macrophages upon infectious and inflammatory stimuli. Mechanistically, <i>Gabra4</i>-mediated signaling led to upregulation of autophagy in macrophages via intracellular calcium release and AMP-activated protein kinase (AMPK) signaling activation, which was required for linking autophagy and antimicrobial responses. Additionally, <i>Gabra4</i> was required to generate mitochondrial reactive oxygen species, thereby triggering autophagy and antimicrobial responses to mycobacteria. Metabolomics analysis showed that <i>Gabra4</i> was critical for glucose metabolism and aerobic glycolysis in macrophages. Our findings demonstrate that myeloid <i>Gabra4</i> coordinates autophagy, inflammation, and immunometabolism to promote innate host defense against pathogenic and dangerous stimuli. <b>Abbreviation</b> AM: Alveolar macrophage; AMPK: AMP-activated protein kinase; ASC: Apoptosis-associated speck-like protein containing a CARD; ATP: Adenosine 5'-triphosphate; BAL: Bronchoalveolar lavage; BCG: <i>Mycobacterium bovis</i> Bacillus Calmette-Guérin; BMDM: Bone marrow-derived macrophage; CCL: CC motif chemokine ligand; CFU: Colony forming unit; CKO: Conditional knock out; CXCL: C-X-C motif ligand; Dpi: Days post-infection; ECAR: Extracellular acidification rate; EGFP: Enhanced green fluorescent protein; FOXO3: Forkhead box O3; GABA: Gamma-aminobutyric acid; GABA_AR: GABA type A receptor; Gabarap: GABA type A receptor-associated protein; Gabarapl1: GABA type A receptor-associated protein like 1; GABRA4: Gamma-aminobutyric acid type A receptor subunit alpha4; HIF-1α: Hypoxia-inducible factor-1 alpha; IL: Interleukin; i.n.: Intranasal; i.p.: Intraperitoneal; LDHA: Lactate dehydrogenase A; LPS: Lipopolysaccharide; Mabc: <i>Mycobacteroides abscessus</i> subsp. <i>abscessus</i>; MOI: Multiplicities of infection; Mtb: <i>Mycobacterium tuberculosis</i>; mtROS: Mitochondrial reactive oxygen species; OCR: Oxygen consumption rate; OXPHOS: Oxidative phosphorylation; PM: Peritoneal macrophage; TNF: Tumor necrosis factor; WT: Wild type.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2181915"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45522059","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":"Regulation of plant autophagy by YWHA/14-3-3 proteins.","authors":"Hua Qi, Yao Wang, Li-Juan Xie, Qing-Qi Lin, Rong-Liang Qiu","doi":"10.1080/27694127.2023.2184015","DOIUrl":"10.1080/27694127.2023.2184015","url":null,"abstract":"<p><p>ATG1/ATG13, a core kinase complex regulator in the macroautophagy/autophagy machinery during autophagosome formation, is modulated in a sophisticated manner by posttranslational ubiquitination to determine proper autophagy levels in eukaryotic cells. However, the mechanisms that regulate the stability and activity of this complex remain elusive. We recently identified two negative regulators of autophagy, 14-3-3λ and 14-3-3k, that help redundantly regulate autophagy by directly associating with SINAT and ATG13s. The specific interaction between the molecular adaptors 14-3-3λ and 14-3-3κ and phosphorylated ATG13a is crucial for SINAT-mediated ubiquitination and degradation of ATG13a, and for maintenance of the ATG1-ATG13 complex. Consistent with the function of 14-3-3s in autophagy, the <i>14-3-3λ 14-3-3κ</i> double mutant exhibits enhanced tolerance to nutrient deprivation with constitutive induction of autophagy. These findings demonstrate that 14-3-3λ and 14-3-3k coordinate with SINATs to regulate both the homeostasis of ATG13 phosphorylation and the induction of autophagy in plants.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2184015"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49528540","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":"External stimulation induces the secretion of autophagosome-like vesicles by B cells.","authors":"Yu-Diao Kuan, Chao-Yuan Tsai, Shuhei Sakakibara, Daron M Standley, Hitoshi Kikutani","doi":"10.1080/27694127.2023.2179287","DOIUrl":"10.1080/27694127.2023.2179287","url":null,"abstract":"<p><p>Macroautophagy/autophagy is a cellular degradation and recycling process that supports cellular homeostasis. Since an autophagosome marker, microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, was found in cell-derived extracellular vesicles (EVs), autophagy may cooperate with EV secretion pathways to control unconventional secretion of intracellular molecules. Several studies have demonstrated that pharmacological inhibition of autophagic turnover and pathogen-induced endolysosomal dysfunction enhanced the secretion of autophagosome-like EVs (ALVs). However, whether external stimulation induces ALV secretion is unclear. Here we showed that co-stimulation with IL-4 and anti-CD40 antibody (IL-4:CD40) enhanced the secretion of LC3-II⁺ALVs compared to co-stimulation by IL-4 and lipopolysaccharide (IL-4:LPS) or by IL4 and anti-IgM antibody in B cells. While IL-4:LPS stimulation accelerated autophagic flux, IL-4:CD40 stimulation reduced autophagosome-lysosome fusion without affecting lysosomal function. Although both IL-4:LPS and IL-4:CD40 induced the expression of similar genes involved in vesicle fusion or transportation, IL-4:CD40 preferentially enhanced the expression of the small GTPase RAB27a compared to IL-4:LPS. Genetic disruption by the CRISPR-Cas9 system revealed that loss of RAB27a membrane-binding ability impaired LC3-II⁺ALV secretion but not ALIX⁺EV secretion in B-lymphoma A20 cells. Additionally, reconstitution of human wild-type RAB27A in RAB27a mutant A20 cells restored LC3-II⁺ALV secretion, indicating that RAB27a controls autophagosome secretion. Furthermore, LC3-II⁺ALVs were found in the sera of tumor-bearing mice and the plasma of healthy human donors. Our findings may provide a role for B-cell secretory autophagy in regulating intercellular communication under various physiological conditions, such as vaccination, pathogen infection, and B-cell lymphoma progression. <b>Abbreviations:</b> ALVs: autophagosome-like vesicles; ATG: autophagy-related; Baf A1: bafilomycin A1; CNX: calnexin; EVs: extracellular vesicles; Ig: immunoglobulin; IL: Interleukin; LC3: microtubule-associated protein 1A/1B-light; LPS: Lipopolysaccharides; MVs: microvesicles; RAB: member RAS oncogene family; TLR: toll-like receptor.</p>","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2179287"},"PeriodicalIF":0.0,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45183223","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":"Lipid-sensor FFAR1 curbs autophagy and mitochondrial respiration in murine retinal angiomatous proliferation.","authors":"Émilie Heckel, Jean-Sébastien Joyal","doi":"10.1080/27694127.2023.2177932","DOIUrl":"10.1080/27694127.2023.2177932","url":null,"abstract":"","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":" ","pages":"2177932"},"PeriodicalIF":0.0,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46653491","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}