Autophagy最新文献

{"title":"Were the autophagosome-lysosome/vacuole fusion models illustrated correctly in the literature?","authors":"Yongheng Liang","doi":"10.1080/15548627.2024.2405954","DOIUrl":"10.1080/15548627.2024.2405954","url":null,"abstract":"<p><p>Exploration of autophagy in different species has become a hotspot in cell biology in the past decades. Macroautophagy (hereafter, autophagy) is the most widely studied type. One of the hallmarks of autophagy is the fusion of the outer membrane (OM) of a closed double-membrane mature autophagosome (AP) with the lysosomal/vacuolar single membrane. Most researchers in the autophagy field agree upon this description. However, AP-lysosome/vacuole fusion models that do not follow this description frequently appear in the literature, even published in some prestigious journals until now. Some of the misrepresented models are from autophagy laboratories with brilliant publication records. These flaws should be addressed as a public announcement in the autophagy field to avoid spreading misinformation. The editors and reviewers are the guardians to ensure correct models.<b>Abbreviations</b>: AP: autophagosome; IM: inner membrane; OM: outer membrane.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309353","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":"Reassessing kinetin's effect on PINK1 and mitophagy.","authors":"Zhong Yan Gan, David Komander, Sylvie Callegari","doi":"10.1080/15548627.2024.2395144","DOIUrl":"https://doi.org/10.1080/15548627.2024.2395144","url":null,"abstract":"<p><p>Substantial evidence indicates that a decline in mitochondrial health contributes to the development of Parkinson disease. Accordingly, therapeutic stimulation of mitophagy, the autophagic turnover of dysfunctional mitochondria, is a promising approach to treat Parkinson disease. An attractive target in such a setting is PINK1, a protein kinase that initiates the mitophagy cascade. Previous reports suggest that PINK1 kinase activity can be enhanced by kinetin triphosphate (KTP), an enlarged ATP analog that acts as an alternate phosphate donor for PINK1 during phosphorylation. However, the mechanism of how KTP could exert such an effect on PINK1 was unclear. In a recent study, we demonstrate that contrary to previous thinking, KTP cannot be used by PINK1. Nucleotide-bound PINK1 structures indicate that KTP would clash with the back of PINK1's ATP binding pocket, and enlarging this pocket by mutagenesis is required to enable PINK1 to use KTP. Strikingly, mutation shifts PINK1's nucleotide preference from ATP to KTP. Similar results could be demonstrated in cells with kinetin, a membrane-permeable precursor of KTP. These results overturn the previously accepted mechanism of how kinetin enhances mitophagy and indicate that kinetin and its derivatives instead function through a currently unidentified mechanism.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334259","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":"Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in <i>Drosophila</i> and vici syndrome patients.","authors":"Celine Deneubourg, Hormos Salimi Dafsari, Simon Lowe, Aitana Martinez-Cotrina, David Mazaud, Seo Hyun Park, Virginia Vergani, Amanda Almacellas Barbanoj, Reza Maroofian, Luisa Averdunk, Ehsan Ghayoor-Karimiani, Sandeep Jayawant, Cyril Mignot, Boris Keren, Renate Peters, Arveen Kamath, Lauren Mattas, Sumit Verma, Arpana Silwal, Felix Distelmaier, Henry Houlden, Gabriele Lignani, Adam Antebi, James Jepson, Heinz Jungbluth, Manolis Fanto","doi":"10.1080/15548627.2024.2405956","DOIUrl":"https://doi.org/10.1080/15548627.2024.2405956","url":null,"abstract":"<p><p>Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms. Vici Syndrome (VS) is the paradigmatic congenital autophagy disorder in humans due to recessive variants in the ectopic P-granules autophagy tethering factor 5 (EPG5) gene that is crucial for autophagosome-lysosome fusion and autophagic clearance. Here, we used Drosophila melanogaster to study the importance of epg5 in development, aging, and seizures. Our data indicate that proteotoxic stress due to impaired autophagic clearance and seizure-like behaviors correlate and are commonly regulated, suggesting that seizures occur as a direct consequence of proteotoxic stress and age-dependent neurodegenerative progression. We provide complementary evidence from EPG5-mutated patients demonstrating an epilepsy phenotype consistent with Drosophila predictions.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334257","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":"SMURF1 mediates damaged lysosomal homeostasis by ubiquitinating PPP3CB to promote the activation of TFEB.","authors":"Qin Xia, Xuan Liu, Lu Zhong, Jun Qu, Lei Dong","doi":"10.1080/15548627.2024.2407709","DOIUrl":"https://doi.org/10.1080/15548627.2024.2407709","url":null,"abstract":"<p><p>The calcium-activated phosphatase PPP3/calcineurin dephosphorylates TFEB (transcription factor EB) to trigger its nuclear translocation and the activation of macroautophagic/autophagic targets. However, the detailed molecular mechanism regulating TFEB activation remains poorly understood. Here, we highlighted the importance of SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) in the activation of TFEB for lysosomal homeostasis. SMURF1 deficiency prevents the calcium-triggered ubiquitination of the catalytic subunit of PPP3/calcineurin in a manner consistent with defective autophagic degradation of damaged lysosomes. Mechanically, PPP3CB/CNA2 plays a bridging role in the recruitment of SMURF1 by LGALS3 (galectin 3) upon lysosome damage. Importantly, PPP3CB increases the dissociation of the N-terminal tail (NT) and C-terminal carbohydrate-recognition domain (CRD) of LGALS3, which may promote the formation of open conformers in a PPP3CB dephosphorylation activity-dependent manner. In addition, PPP3CB is ubiquitinated at lysine 146 by the recruited SMURF1 in response to intracellular calcium stimulation. The K63-linked ubiquitination of PPP3CB enhances the recruitment of TFEB. Moreover, TFEB directly interacts with both PPP3CB and the regulatory subunit PPP3R1 which facilitate the conformational correction of TFEB for its activation for the transcription of TFEB-targeted genes. Altogether, our results highlighted a critical mechanism for the regulation of PPP3/calcineurin activity via its ubiquitin ligase SMURF1 in response to lysosomal membrane damage, which may account for a potential target for the treatment of stress-related diseases.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334260","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":"Quality control of mitochondria involves lysosomes in multiple definitive ways.","authors":"Xiaowen Ma, Wen-Xing Ding","doi":"10.1080/15548627.2024.2408712","DOIUrl":"https://doi.org/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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334258","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":"ATP6V1D drives hepatocellular carcinoma stemness and progression via both lysosome acidification-dependent and -independent mechanisms.","authors":"Zhijie Xu, Ruiyang Liu, Haoying Ke, Fuyuan Xu, Pengfei Yang, Weiyu Zhang, Yi Zhan, Zhiju Zhao, Fei Xiao","doi":"10.1080/15548627.2024.2406186","DOIUrl":"https://doi.org/10.1080/15548627.2024.2406186","url":null,"abstract":"<p><p>Metabolic reprogramming is pivotal in cancer stem cell (CSC) self-renewal. However, the intricate regulatory mechanisms governing the crosstalk between metabolic reprogramming and liver CSCs remain elusive. Here, using a metabolic CRISPR-Cas9 knockout screen, we identify ATP6V1D, a subunit of the vacuolar-type H⁺-translocating ATPase (V-ATPase), as a key metabolic regulator of hepatocellular carcinoma (HCC) stemness. Elevated ATP6V1D expression correlates with poor clinical outcomes in HCC patients. ATP6V1D knockdown inhibits HCC stemness and malignant progression both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, ATP6V1D enhances HCC stemness and progression by maintaining macroautophagic/autophagic flux. Specifically, ATP6V1D not only promotes lysosomal acidification, but also enhances the interaction between CHMP4B and IST1 to foster ESCRT-III complex assembly, thereby facilitating autophagosome-lysosome fusion to maintain autophagic flux. Moreover, silencing CHMP4B or IST1 attenuates HCC stemness and progression. Notably, low-dose bafilomycin A₁ targeting the V-ATPase complex shows promise as a potential therapeutic strategy for HCC. In conclusion, our study highlights the critical role of ATP6V1D in driving HCC stemness and progression via the autophagy-lysosomal pathway, providing novel therapeutic targets and approaches for HCC treatment.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334256","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":"Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy.","authors":"Alexandre Leytens, Rocío Benítez-Fernández, Carlos Jiménez-García, Carole Roubaty, Michael Stumpe, Patricia Boya, Jörn Dengjel","doi":"10.1080/15548627.2024.2396792","DOIUrl":"10.1080/15548627.2024.2396792","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Macroautophagy/autophagy is a constitutively active catabolic lysosomal degradation pathway, often found dysregulated in human diseases. It is often considered to act in a cytoprotective manner and is commonly upregulated in cells undergoing stress. Its initiation is regulated at the protein level and does not require &lt;i&gt;de novo&lt;/i&gt; protein synthesis. Historically, autophagy has been regarded as nonselective; however, it is now clear that different stimuli can lead to the selective degradation of cellular components via selective autophagy receptors (SARs). Due to its selective nature and the existence of multiple degradation pathways potentially acting in concert, monitoring of autophagy flux, &lt;i&gt;i.e&lt;/i&gt;. selective autophagy-dependent protein degradation, should address this complexity. Here, we introduce a targeted proteomics approach monitoring abundance changes of 37 autophagy-related proteins covering process-relevant proteins such as the initiation complex and the Atg8-family protein lipidation machinery, as well as most known SARs. We show that proteins involved in autophagosome biogenesis are upregulated and spared from degradation under autophagy-inducing conditions in contrast to SARs, in a cell-line dependent manner. Classical bulk stimuli such as nutrient starvation mainly induce degradation of ubiquitin-dependent soluble SARs and not of ubiquitin-independent, membrane-bound SARs. In contrast, treatment with the iron chelator deferiprone leads to the degradation of ubiquitin-dependent and -independent SARs linked to mitophagy and reticulophagy/ER-phagy. Our approach is automatable and supports large-scale screening assays paving the way to (pre)clinical applications and monitoring of specific autophagy flux.&lt;b&gt;Abbreviation:&lt;/b&gt; AMBRA1: autophagy and beclin 1 regulator 1; ATG: autophagy related; BafA1: bafilomycin A&lt;sub&gt;1&lt;/sub&gt;; BNIP1: BCL2 interacting protein 1; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3-like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCPG1: cell cycle progression 1; CV: coefficients of variations; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DFP: deferiprone; ER: endoplasmic reticulum; FKBP8: FKBP prolyl isomerase 8; GABARAPL: GABA type A receptor associated protein like; LC: liquid chromatography; LOD: limit of detection; LOQ: limit of quantification; MAP1LC3: microtubule associated protein 1 light chain 3; MS: mass spectrometry; NCOA4: nuclear receptor coactivator 4; NBR1: NBR1 autophagy cargo receptor; NUFIP1: nuclear FMR1 interacting protein 1; OPTN: optineurin; PHB2: prohibitin 2; PNPLA2/ATGL: patatin like phospholipase domain containing 2; POI: protein of interest; PTM: posttranslational modification; PRM: parallel reaction monitoring; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RETREG1/FAM134B: reticulophagy regulator 1; RPS6KB1: ribosomal protein S6 kinase B1; RTN3: reticulon 3; SARs: selective autophagy receptors; SQSTM1/p62: sequestosome 1; STBD1: sta","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156931","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":"MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.","authors":"Zhigang Zhang, Shuai Chen, Shirui Jun, Xirong Xu, Yuchuan Hong, Xifei Yang, Liangyu Zou, You-Qiang Song, Yu Chen, Jie Tu","doi":"10.1080/15548627.2024.2395727","DOIUrl":"10.1080/15548627.2024.2395727","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Individuals with genetic elimination of &lt;i&gt;MLKL&lt;/i&gt; (mixed lineage kinase domain like pseudokinase) exhibit an increased susceptibility to neurodegenerative diseases like Alzheimer disease (AD). However, the mechanism is not yet fully understood. Here, we observed significant compromise in macroautophagy/autophagy in the brains of &lt;i&gt;mlkl&lt;/i&gt; knockout (KO) mice, as evidenced by the downregulation of BECN1/Beclin1 and ULK1 (unc-51 like autophagy activating kinase 1). We identified UBA52 (ubiquitin A-52 residue ribosomal protein fusion product 1) as the binding partner of MLKL under physiological conditions. Loss of &lt;i&gt;Mlkl&lt;/i&gt; induced a decrease in ubiquitin levels by preventing UBA52 cleavage. Furthermore, we demonstrated that the deubiquitinase (DUB) USP7 (ubiquitin specific peptidase 7) mediates the processing of UBA52, which is regulated by MLKL. Moreover, our results indicated that the reduction of BECN1 and ULK1 upon &lt;i&gt;Mlkl&lt;/i&gt; loss is attributed to a decrease in their lysine 63 (K63)-linked polyubiquitination. Additionally, single-nucleus RNA sequencing revealed that the loss of &lt;i&gt;Mlkl&lt;/i&gt; resulted in the disruption of multiple neurodegenerative disease-related pathways, including those associated with AD. These results were consistent with the observation of cognitive impairment in &lt;i&gt;mlkl&lt;/i&gt; KO mice and exacerbation of AD pathologies in an AD mouse model with &lt;i&gt;mlkl&lt;/i&gt; deletion. Taken together, our findings demonstrate that MLKL-USP7-UBA52 signaling is required for autophagy in brain through maintaining ubiquitin homeostasis, and highlight the contribution of &lt;i&gt;Mlkl&lt;/i&gt; loss-induced ubiquitin deficits to the development of neurodegeneration. Thus, the maintenance of adequate levels of ubiquitin may provide a novel perspective to protect individuals from multiple neurodegenerative diseases through regulating autophagy.&lt;b&gt;Abbreviations&lt;/b&gt;: 4HB: four-helix bundle; AAV: adeno-associated virus; AD: Alzheimer disease; AIF1: allograft inflammatory factor 1; APOE: apolipoprotein E; APP: amyloid beta precursor protein; Aβ: amyloid β; BECN1: beclin 1; co-IP: co-immunoprecipitation; DEGs: differentially expressed genes; DLG4: discs large MAGUK scaffold protein 4; DUB: deubiquitinase; EBSS: Earle's balanced salt solution; GFAP: glial fibrillary acidic protein; HRP: horseradish peroxidase; IL1B: interleukin 1 beta; IL6: interleukin 6; IPed: immunoprecipitated; KEGG: Kyoto Encyclopedia of Genes and Genomes; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MLKL: mixed lineage kinase domain like pseudokinase; NSA: necrosulfonamide; OPCs: oligodendrocyte precursor cells; PFA: paraformaldehyde; PsKD: pseudo-kinase domain; SYP: synaptophysin; UB: ubiquitin; UBA52: ubiquitin A-52 residue ribosomal protein fusion product 1; UCHL3: ubiquitin C-terminal hydrolase L3; ULK1: unc-51 like autophagy activating kinase 1; UMAP: uniform manifold approximation and projection; UPS: ubiquitin-proteasome system; USP7: ubiquitin specif","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082829","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":"Correction.","authors":"","doi":"10.1080/15548627.2024.2401222","DOIUrl":"https://doi.org/10.1080/15548627.2024.2401222","url":null,"abstract":"","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303282","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":"Bunyavirus SFTSV nucleoprotein exploits TUFM-mediated mitophagy to impair antiviral innate immunity.","authors":"Wen-Kang Zhang, Jia-Min Yan, Min Chu, Bang Li, Xiao-Lan Gu, Ze-Zheng Jiang, Ze-Min Li, Pan-Pan Liu, Tian-Mei Yu, Chuan-Min Zhou, Xue-Jie Yu","doi":"10.1080/15548627.2024.2393067","DOIUrl":"10.1080/15548627.2024.2393067","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome is an emerging viral hemorrhagic fever caused by a tick-borne bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), with a high case fatality. We previously found that SFTSV nucleoprotein (NP) induces macroautophagy/autophagy to facilitate virus replication. However, the role of NP in antagonizing host innate immunity remains unclear. Mitophagy, a selected form of autophagy, eliminates damaged mitochondria to maintain mitochondrial homeostasis. Here, we demonstrate that SFTSV NP triggers mitophagy to degrade MAVS (mitochondrial antiviral signaling protein), thereby blocking MAVS-mediated antiviral signaling to escape the host immune response. Mechanistically, SFTSV NP translocates to mitochondria by interacting with TUFM (Tu translation elongation factor, mitochondrial), and mediates mitochondrial sequestration into phagophores through interacting with LC3, thus inducing mitophagy. Notably, the N-terminal LC3-interacting region (LIR) motif of NP is essential for mitophagy induction. Collectively, our results demonstrated that SFTSV NP serves as a novel virulence factor, inducing TUFM-mediated mitophagy to degrade MAVS and evade the host immune response.<b>Abbreviation:</b> 3-MA: 3-methyladenine; ACTB: actin beta; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole, dihydrochloride; DMSO: dimethyl sulfoxide; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GFP: green fluorescent protein; HTNV: Hantan virus; IAV: influenza A virus; IFN: interferon; LAMP1: lysosomal associated membraneprotein 1; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule associatedprotein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; Mdivi-1: mitochondrial division inhibitor 1; MOI: multiplicity of infection; MT-CO2/COXII: mitochondrially encoded cytochrome C oxidase II; NP: nucleoprotein; NSs: nonstructural proteins; poly(I:C): polyinosinic:polycytidylic acid; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SFTSV: severe fever withthrombocytopenia syndrome virus; TCID50: 50% tissue culture infectiousdose; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20:translocase of outer mitochondrial membrane 20; TUFM: Tu translation elongationfactor, mitochondrial.</p>","PeriodicalId":93893,"journal":{"name":"Autophagy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074822","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}