Autophagy最新文献

{"title":"FOXO-regulated DEAF1 controls muscle regeneration through autophagy.","authors":"Kah Yong Goh, Wen Xing Lee, Sze Mun Choy, Gopal Krishnan Priyadarshini, Kenon Chua, Qian Hui Tan, Shin Yi Low, Hui San Chin, Chee Seng Wong, Shu-Yi Huang, Nai Yang Fu, Jun Nishiyama, Nathan Harmston, Hong-Wen Tang","doi":"10.1080/15548627.2024.2374693","DOIUrl":"10.1080/15548627.2024.2374693","url":null,"abstract":"<p><p>The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a new regulator of muscle regeneration, Deaf1 (Deformed epidermal autoregulatory factor-1) - a transcriptional factor downstream of foxo signaling. We showed that <i>Deaf1</i> is transcriptionally repressed by FOXOs and that DEAF1 targets to <i>Pik3c3</i> and <i>Atg16l1</i> promoter regions and suppresses their expression. <i>Deaf1</i> depletion therefore induces macroautophagy/autophagy, which in turn blocks MuSC survival and differentiation. In contrast, <i>Deaf1</i> overexpression inactivates autophagy in MuSCs, leading to increased protein aggregation and cell death. The fact that <i>Deaf1</i> depletion and its overexpression both lead to defects in muscle regeneration highlights the importance of fine tuning DEAF1-regulated autophagy during muscle regeneration. We further showed that <i>Deaf1</i> expression is altered in aging and cachectic MuSCs. Manipulation of <i>Deaf1</i> expression can attenuate muscle atrophy and restore muscle regeneration in aged mice or mice with cachectic cancers. Together, our findings unveil an evolutionarily conserved role for DEAF1 in muscle regeneration, providing insights into the development of new therapeutic strategies against muscle atrophy.<b>Abbreviations</b>: DEAF1: Deformed epidermal autoregulatory factor-1; FOXO: Forkhead box O; MuSC: Muscle Stem Cell; PAX7: Paired box 7; PIK3C3: Phosphatidylinositol 3-kinase catalytic subunit type 3.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2632-2654"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499845","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":"PRRSV utilizes MALT1-regulated autophagy flux to switch virus spread and reserve.","authors":"Han Gu, He Qiu, Haotian Yang, Zhuofan Deng, Shengkun Zhang, Liuyang Du, Fang He","doi":"10.1080/15548627.2024.2386195","DOIUrl":"10.1080/15548627.2024.2386195","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) is a major swine pathogen, which can survive host antiviral immunity with various mechanisms. PRRSV infection induces macroautophagy/autophagy, facilitating virus replication. MALT1, a central immune regulator, was manipulated by PRRSV to optimize viral infection at different stages of the virus cycle. In this study, the key role of MALT1 in autophagy regulation during PRRSV infection was characterized, enlightening the role of autophagy flux in favor of virus spread and persistent infection. PRRSV-induced autophagy was confirmed to facilitate virus proliferation. Furthermore, autophagic fusion was dynamically regulated during PRRSV infection. Importantly, PRRSV-induced MALT1 facilitated autophagosome-lysosome fusion and autolysosome formation, thus contributing to autophagy flux and virus proliferation. Mechanically, MALT1 regulated autophagy via mediating MTOR-ULK1 and -TFEB signaling and affecting lysosomal homeostasis. MALT1 inhibition by inhibitor Mi-2 or RNAi induced lysosomal membrane permeabilization (LMP), leading to the block of autophagic fusion. Further, MALT1 overexpression alleviated PRRSV-induced LMP via inhibiting ROS generation. In addition, blocking autophagy flux suppressed virus release significantly, indicating that MALT1-maintained complete autophagy flux during PRRSV infection favors successful virus spread and its proliferation. In contrast, autophagosome accumulation upon MALT1 inhibition promoted PRRSV reserve for future virus proliferation once the autophagy flux recovers. Taken together, for the first time, these findings elucidate that MALT1 was utilized by PRRSV to regulate host autophagy flux, to determine the fate of virus for either proliferation or reserve.<b>Abbreviations</b>: 3-MA: 3-methyladenine; BafA1: bafilomycin A₁; BFP/mBFP: monomeric blue fluorescent protein; CQ: chloroquine; DMSO: dimethyl sulfoxide; dsRNA: double-stranded RNA; GFP: green fluorescent protein; hpi: hours post infection; IFA: indirect immunofluorescence assay; LAMP1: lysosomal associated membrane protein 1; LGALS3: galectin 3; LLOMe: L-leucyl-L-leucine-methyl ester; LMP: lysosomal membrane permeabilization; mAb: monoclonal antibody; MALT1: MALT1 paracaspase; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; NFKB/NF-κB: nuclear factor kappa B; nsp: nonstructural protein; ORF: open reading frame; pAb: polyclonal antibody; PRRSV: porcine reproductive and respiratory syndrome virus; PRRSV-N: PRRSV nucleocapsid protein; Rapa: rapamycin; RFP: red fluorescent protein; ROS: reactive oxygen species; SBI: SBI-0206965; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID₅₀: 50% tissue culture infective dose; TFEB: transcription factor EB; ULK1: unc-51 like autophagy activating kinase 1.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2697-2718"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857388","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 surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity.","authors":"Sebastian J Hofer, Ioanna Daskalaki, Mahmoud Abdellatif, Ulrich Stelzl, Simon Sedej, Nektarios Tavernarakis, Guido Kroemer, Frank Madeo","doi":"10.1080/15548627.2024.2396793","DOIUrl":"10.1080/15548627.2024.2396793","url":null,"abstract":"<p><p>Acute nutrient deprivation (fasting) causes an immediate increase in spermidine biosynthesis in yeast, flies, mice and humans, as corroborated in four independent clinical studies. This fasting-induced surge in spermidine constitutes the critical first step of a phylogenetically conserved biochemical cascade that leads to spermidine-dependent hypusination of EIF5A (eukaryotic translation initiation factor 5A), which favors the translation of the pro-macroautophagic/autophagic TFEB (transcription factor EB), and hence an increase in autophagic flux. We observed that genetic or pharmacological inhibition of the spermidine increase by inhibition of ODC1 (ornithine decarboxylase 1) prevents the pro-autophagic and antiaging effects of fasting in yeast, nematodes, flies and mice. Moreover, knockout or knockdown of the enzymes required for EIF5A hypusination abolish fasting-mediated autophagy enhancement and longevity extension in these organisms. Of note, autophagy and longevity induced by rapamycin obey the same rule, meaning that they are tied to an increase in spermidine synthesis. These findings indicate that spermidine is not only a \"caloric restriction mimetic\" in the sense that its supplementation mimics the beneficial effects of nutrient deprivation on organismal health but that it is also an obligatory downstream effector of the antiaging effects of fasting and rapamycin.<b>Abbreviation</b>: EIF5A: eukaryotic translation initiation factor 5A; IGF1: insulin like growth factor 1; MTOR: mechanistic target of rapamycin kinase; ODC1: ornithine decarboxylase 1; TFEB: transcription factor EB.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2824-2826"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115909","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":"Should it stay or should it go: gap junction protein GJA1/Cx43 conveys damaged lysosomes to the cell periphery to potentiate exocytosis.","authors":"Neuza Domingues, Teresa Ribeiro-Rodrigues, Henrique Girão","doi":"10.1080/15548627.2024.2408711","DOIUrl":"10.1080/15548627.2024.2408711","url":null,"abstract":"<p><p>GJA1/Cx43 (gap junction protein alpha 1) has long been associated with gap junctions-mediated communication between adjacent cells. However, recent data have defied this concept, with studies implicating GJA1 in other biological processes, such as macroautophagy/autophagy regulation, mitochondrial activity and extracellular vesicles biology. In our recent study we unveiled an additional role played by GJA1 in lysosomal trafficking. We demonstrate that GJA1 promotes the exocytosis of damaged lysosomes, through a mechanism that relies on ACTR2/ARP2-ACTR3/ARP3-dependent actin remodeling. Our findings ascribe to GJA1 an important role during pathogen infection and lysosomal storage disorders, favoring the release of dysfunctional lysosomes.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2816-2818"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482861","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":"Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.","authors":"Jiao Liu, Yichun Wang, Ling Zeng, Chunhua Yu, Rui Kang, Daniel J Klionsky, Jianxin Jiang, Daolin Tang","doi":"10.1080/15548627.2024.2372215","DOIUrl":"10.1080/15548627.2024.2372215","url":null,"abstract":"<p><p>Sepsis, a life-threatening condition resulting from a dysregulated response to pathogen infection, poses a significant challenge in clinical management. Here, we report a novel role for the autophagy receptor NCOA4 in the pathogenesis of sepsis. Activated macrophages and monocytes secrete NCOA4, which acts as a mediator of septic death in mice. Mechanistically, lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, induces NCOA4 secretion through autophagy-dependent lysosomal exocytosis mediated by ATG5 and MCOLN1. Moreover, bacterial infection with <i>E. coli</i> or <i>S. enterica</i> leads to passive release of NCOA4 during GSDMD-mediated pyroptosis. Upon release, extracellular NCOA4 triggers the activation of the proinflammatory transcription factor NFKB/NF-κB by promoting the degradation of NFKBIA/IκB molecules. This process is dependent on the pattern recognition receptor AGER, rather than TLR4. <i>In vivo</i> studies employing endotoxemia and polymicrobial sepsis mouse models reveal that a monoclonal neutralizing antibody targeting NCOA4 or AGER delays animal death, protects against organ damage, and attenuates systemic inflammation. Furthermore, elevated plasma NCOA4 levels in septic patients, particularly in non-survivors, correlate positively with the sequential organ failure assessment score and concentrations of lactate and proinflammatory mediators, such as TNF, IL1B, IL6, and HMGB1. These findings demonstrate a previously unrecognized role of extracellular NCOA4 in inflammation, suggesting it as a potential therapeutic target for severe infectious diseases. <b>Abbreviation:</b> BMDMs: bone marrow-derived macrophages; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; ELISA: enzyme-linked immunosorbent assay; LPS: lipopolysaccharide; NO: nitric oxide; SOFA: sequential organ failure assessment.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2616-2631"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447785","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":"An interplay between biomolecular condensates and SNARE proteins regulates plant autophagy.","authors":"Ruixi Li, Lei Pang","doi":"10.1080/15548627.2024.2408188","DOIUrl":"10.1080/15548627.2024.2408188","url":null,"abstract":"<p><p>A recent study in our group reports a new \"condensates to VPS41-associated phagic vacuole (VAPVs) conversion pathway\" that is essential for macroautophagy/autophagy degradation in plant cells. Here, we compare the autophagy process between plants and other eukaryotic systems and discuss the potential roles of biomolecular condensates and synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins in plant autophagy.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2833-2835"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334255","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":"Quality control of mitochondria involves lysosomes in multiple definitive ways.","authors":"Xiaowen Ma, Wen-Xing Ding","doi":"10.1080/15548627.2024.2408712","DOIUrl":"10.1080/15548627.2024.2408712","url":null,"abstract":"<p><p>Mitochondria are crucial organelles in maintaining cellular homeostasis. They are involved in processes such as energy production, metabolism of lipids and glucose, and cell death regulation. Mitochondrial dysfunction can lead to various health issues such as aging, cancer, neurodegenerative diseases, and chronic liver diseases. While mitophagy is the main process for getting rid of excess or damaged mitochondria, there are additional mechanisms for preserving mitochondrial quality. One such alternative mechanism we have discovered is a hybrid organelle called mitochondrial-lysosome-related-organelle (MLRO), which functions independently of the typical autophagy process. More recently, another type of vesicle called vesicle derived from the inner mitochondrial membrane (VDIM) has been identified to break down the inner mitochondrial membrane without involving the standard autophagy pathway. In this article, we will delve into the similarities and differences between MLRO and VDIM, including their structure, regulation, and relevance to human diseases.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2599-2601"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334258","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":"ZDHHC7-mediated <i>S</i>-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation.","authors":"Fujing Wei, Yu Wang, Jia Yao, Ligang Mei, Xue Huang, Hesheng Kong, Jing Chen, Xiaorong Chen, Lu Liu, Zhuolin Wang, Jiaxin Wang, Jiong Song, Eryan Kong, Aimin Yang","doi":"10.1080/15548627.2024.2386915","DOIUrl":"10.1080/15548627.2024.2386915","url":null,"abstract":"<p><p>Macroautophagy/autophagy is a fundamental cellular catabolic process that delivers cytoplasmic components into double-membrane vesicles called autophagosomes, which then fuse with lysosomes and their contents are degraded. Autophagy recycles cytoplasmic components, including misfolded proteins, dysfunctional organelles and even microbial invaders, thereby playing an essential role in development, immunity and cell death. Autophagosome formation is the main step in autophagy, which is governed by a set of ATG (autophagy related) proteins. ATG16L1 interacts with ATG12-ATG5 conjugate to form an ATG12-ATG5-ATG16L1 complex. The complex acts as a ubiquitin-like E3 ligase that catalyzes the lipidation of MAP1LC3/LC3 (microtubule associated protein 1 light chain 3), which is crucial for autophagosome formation. In the present study, we found that ATG16L1 was subject to <i>S</i>-palmitoylation on cysteine 153, which was catalyzed by ZDHHC7 (zinc finger DHHC-type palmitoyltransferase 7). We observed that re-expressing ATG16L1 but not the <i>S</i>-palmitoylation-deficient mutant ATG16L1^C153S rescued a defect in the lipidation of LC3 and the formation of autophagosomes in <i>ATG16L1</i>-KO (knockout) HeLa cells. Furthermore, increasing ATG16L1 <i>S</i>-palmitoylation by ZDHHC7 expression promoted the production of LC3-II, whereas reducing ATG16L1 <i>S</i>-palmitoylation by <i>ZDHHC7</i> deletion inhibited the LC3 lipidation process and autophagosome formation. Mechanistically, the addition of a hydrophobic 16-carbon palmitoyl group on Cys153 residue of ATG16L1 enhances the formation of ATG16L1-WIPI2B complex and ATG16L1-RAB33B complex on phagophore, thereby facilitating the LC3 lipidation process and autophagosome formation. In conclusion, <i>S</i>-palmitoylation of ATG16L1 is essential for the lipidation process of LC3 and the formation of autophagosomes. Our research uncovers a new regulatory mechanism of ATG16L1 function in autophagy.<b>Abbreviation</b>: ABE: acyl-biotin exchange; ATG: autophagy related; Baf-A1: bafilomycin A₁; 2-BP: 2-bromopalmitate; CCD: coiled-coil domain; co-IP: co-immunoprecipitation; CQ: chloroquine; EBSS: Earle's balanced salt solution; HAM: hydroxylamine; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NP-40: Nonidet P-40; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; PtdIns3K-C1: class III phosphatidylinositol 3-kinase complex I; PTM: post-translational modification; RAB33B: RAB33B, member RAS oncogene family; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SDS: sodium dodecyl sulfate; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscope; WD: tryptophan and aspartic acid; WIPI2B: WD repeat domain, phosphoinositide interacting 2B; WT: wild-type; ZDHHC: zinc finger DHHC-type palmitoyltransferase.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2719-2737"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861915","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":"RAB37-mediated autophagy guards ovarian homeostasis and function.","authors":"Xu Xu, Mengxin Hu, Ruhong Ying, Juan Zou, Zhuoyue Du, Lan Lin, Tian Lan, Haoyu Wang, Yu Hou, Hanhua Cheng, Rongjia Zhou","doi":"10.1080/15548627.2024.2389568","DOIUrl":"10.1080/15548627.2024.2389568","url":null,"abstract":"<p><p>Loss of ovarian homeostasis is associated with ovary dysfunction and female diseases; however, the underlying mechanisms responsible for the establishment of homeostasis and its function in the ovary have not been fully elucidated. Here, we showed that conditional knockout of <i>Rab37</i> in oocytes impaired macroautophagy/autophagy proficiency in the ovary and interfered with follicular homeostasis and ovary development in mice. Flunarizine treatment upregulated autophagy, thus rescuing the impairment of follicular homeostasis and ovarian dysfunction in <i>rab37</i> knockout mice by reprogramming of homeostasis. Notably, both the E2F1 and EGR2 transcription factors synergistically activated <i>Rab37</i> transcription and promoted autophagy. Thus, RAB37-mediated autophagy ensures ovary function by maintaining ovarian homeostasis.<b>Abbreviations:</b> AMH: anti-Mullerian hormone; ATG: autophagy related; BECN1: beclin 1; cKO: conditional knockout; Cre: cyclization recombination enzyme; dpp: days postpartum; E2: estradiol; E2F1: E2F transcription factor 1; EBF1: EBF transcription factor 1; EGR2: early growth response 2; FSH: follicle stimulating hormone; LH: luteinizing hormone; mpp: months postpartum; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; RAB37: RAB37, member RAS oncogene family; SQSTM1: sequestosome 1; TFEB: transcription factor EB; <i>Zp3</i>: zona pellucida glycoprotein 3.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2738-2751"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903916","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":"Dual roles of AtNBR1 in regulating selective autophagy <i>via</i> liquid-liquid phase separation and recognition of non-ubiquitinated substrates in Arabidopsis.","authors":"He Yan, Ao Qi, Zhen Lu, Zhengtao You, Ziheng Wang, Haiying Tang, Xinghai Li, Qiao Xu, Xun Weng, Xiaojuan Du, Lifeng Zhao, Hao Wang","doi":"10.1080/15548627.2024.2391725","DOIUrl":"10.1080/15548627.2024.2391725","url":null,"abstract":"<p><p>Selective macroautophagy/autophagy in metazoans involves the conserved receptors NBR1 and SQSTM1/p62. Both autophagy receptors manage ubiquitinated cargo recognition, while SQSTM1 has an additional, distinct role of facilitating liquid-liquid phase separation (LLPS) during autophagy. Given that plants lack SQSTM1, it is postulated that plant NBR1 may combine activities of both metazoan NBR1 and SQSTM1. However, the precise mechanism by which plant NBR1 recognizes non-ubiquitinated substrates and its ability to undergo LLPS during selective autophagy remain elusive. Here, we implicate both the ZZ-type zinc finger motif and the four-tryptophan domain of Arabidopsis NBR1 (AtNBR1) in the recognition of non-ubiquitinated cargo proteins. Additionally, we reveal that AtNBR1 indeed undergoes LLPS prior to ATG8-mediated autophagosome formation, crucial for heat stress resistance in Arabidopsis. Our findings unveil the dual roles of AtNBR1 in both cargo recognition and LLPS during plant autophagy and advance our understanding of NBR1-mediated autophagy in plants compared to metazoans.<b>Abbreviations</b>: ATG8: autophagy 8; Co-IP: co-immunoprecipitation; EXO70E2: exocyst subunit EXO70 family protein E2; FRAP: fluorescence recovery after photobleaching; FW domain: four-tryptophan domain; GFP: green fluorescent protein; HS: heat stress; LLPS: liquid-liquid phase separation; LIR: LC3-interacting region; NBR1: next to BRCA1 gene 1; PAS: phagophore assembly site; PB1 domain: Phox and Bem1 domain; RFP: red fluorescent protein; ROF1: rotamase FKBP 1; SARs: selective autophagy receptors; UBA domain: ubiquitin-associated domain; Y2H: yeast two-hybrid; ZZ domain: ZZ-type zinc finger motif domain.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":" ","pages":"2804-2815"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006039","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}