IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-05-12 DOI: 10.1080/15548627.2023.2210446

Shan-Ying Wu, Yi-Ching Wang, Roberto Zuchini, Kai-Ying Lan, Hsiao-Sheng Liu, Sheng-Hui Lan

{"title":"Secretory autophagy-promoted cargo exocytosis requires active RAB37.","authors":"Shan-Ying Wu, Yi-Ching Wang, Roberto Zuchini, Kai-Ying Lan, Hsiao-Sheng Liu, Sheng-Hui Lan","doi":"10.1080/15548627.2023.2210446","DOIUrl":"10.1080/15548627.2023.2210446","url":null,"abstract":"RAB37 GTPase regulates cargo exocytosis by cycling between an inactive GDP-bound form and an active GTP-bound form. We reveal that RAB37 simultaneously regulates autophagy activation and tissue inhibitor of metalloproteinase 1 (TIMP1) secretion in lung cancer cells under starvation conditions. TIMP1, an inflammatory cytokine, is a known inhibitory molecule of matrix metalloproteinases matrix metalloproteinase 9 and suppresses the mobility of lung cancer cells both in vitro and in vivo through conventional exocytosis under serum-free conditions. Notably, we disclosed that secretory autophagy participates in TIMP1 secretion in a RAB37- and Sec22b-dependent manner. Sec22b, a SNARE family protein, participates in vesicle and membrane fusion of secretory autophagy. Knockdown of Sec22b decreased TIMP1 secretion and cell motility but did not affect cell proliferation under starvation conditions. We confirmed that starvation-activated RAB37 accompanied by Sec22b is essential for secretory autophagy to further enhance TIMP1 exocytosis. We further use an off-label drug amiodarone to demonstrate that autophagy induction facilitates TIMP1 secretion and suppresses the motility and metastasis of lung cancer cells in a RAB37-dependent manner in the lung-to-lung mouse model. In conclusion, we demonstrated that the RAB37 activation plays a pivotal regulatory role in secretory autophagy for TIMP1 secretion in lung cancer.Abbreviations: ATG: autophagy-related gene; GDP: guanosine diphosphate; GTP: guanosine triphosphate; LC3: microtubule-associated protein 1A/1B-light chain 3; SNARE: soluble N-ethylmaleimide-sensitive-factor attachment protein receptor; TIMP1: tissue inhibitor matrix metalloproteinase 1.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"933-934"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446150","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}

引用次数: 0

Microglial cytokines poison neuronal autophagy via CCR5, a druggable target. 小胶质细胞因子通过药物靶点 CCR5 毒害神经元自噬

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-26 DOI: 10.1080/15548627.2023.2221921

Beatrice Paola Festa, Farah H Siddiqi, Maria Jimenez-Sanchez, David C Rubinsztein

{"title":"Microglial cytokines poison neuronal autophagy via CCR5, a druggable target.","authors":"Beatrice Paola Festa, Farah H Siddiqi, Maria Jimenez-Sanchez, David C Rubinsztein","doi":"10.1080/15548627.2023.2221921","DOIUrl":"10.1080/15548627.2023.2221921","url":null,"abstract":"In the prodromal phase of neurodegenerative diseases, microglia switch to an activated state resulting in increased secretion of pro-inflammatory factors. We reported that C - C chemokine ligand 3 (CCL3), C - C chemokine ligand 4 (CCL4) and C - C chemokine ligand 5 (CCL5) contained in the secretome of activated microglia inhibit neuronal autophagy via a non-cell autonomous mechanism. These chemokines bind and activate neuronal C - C chemokine receptor type 5 (CCR5), which, in turn, promotes phosphoinositide 3-kinase (PI3K) - protein kinase B (PKB, or AKT) - mammalian target of rapamycin complex 1 (mTORC1) pathway activation, which inhibits autophagy, thus causing the accumulation of aggregate-prone proteins in the cytoplasm of neurons. The levels of CCR5 and its chemokine ligands are increased in the brains of pre-manifesting Huntington disease (HD) and tauopathy mouse models. CCR5 accumulation might be due to a self-amplifying mechanism, since CCR5 is a substrate of autophagy and CCL5-CCR5-mediated autophagy inhibition impairs CCR5 degradation. Furthermore, pharmacological, or genetic inhibition of CCR5 rescues mTORC1-autophagy dysfunction and improves neurodegeneration in HD and tauopathy mouse models, suggesting that CCR5 hyperactivation is a pathogenic signal driving the progression of these diseases.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"949-951"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9685360","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}

引用次数: 0

Autophagy fuels mitochondrial function through regulation of iron metabolism in pancreatic cancer. 自噬通过调节癌症中的铁代谢来促进线粒体功能。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-13 DOI: 10.1080/15548627.2023.2223473

Subhadip Mukhopadhyay, Joel Encarnacion-Rosado, Alec C Kimmelman

{"title":"Autophagy fuels mitochondrial function through regulation of iron metabolism in pancreatic cancer.","authors":"Subhadip Mukhopadhyay, Joel Encarnacion-Rosado, Alec C Kimmelman","doi":"10.1080/15548627.2023.2223473","DOIUrl":"10.1080/15548627.2023.2223473","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of any cancer in the United States. Our previous work has shown that autophagy can promote PDAC progression. We recently established the importance of autophagy in regulating bioavailable iron to control mitochondrial metabolism in PDAC. We found that inhibition of autophagy in PDAC leads to mitochondrial dysfunction due to abrogation of succinate dehydrogenase complex iron sulfur subunit B (SDHB) expression. Additionally, we observed that cancer-associated fibroblasts (CAFs) can provide iron to autophagy-inhibited PDAC tumor cells, thereby increasing their resistance to autophagy inhibition. To impede such metabolic compensation, we used a low iron diet together with autophagy inhibition and demonstrated a significant improvement of tumor response in syngeneic PDAC models.Abbreviations: PDAC: Pancreatic ductal adenocarcinoma; CAFs: cancer-associated fibroblasts; SDHB: succinate dehydrogenase complex iron sulfur subunit B; ISCA1: iron sulfur cluster assembly protein 1; FPN: ferroportin; LIP: labile iron pool; FAC: ferric ammonium chloride; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation, IL6: interleukin 6; Fe-S: iron sulfur; ATP: adenosine triphosphate.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"963-964"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9618570","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}

引用次数: 0

ATG8 proteins are co-factors for human dopaminergic neuronal transcriptional control: implications for neuronal resilience in Parkinson disease. ATG8 蛋白是人类多巴胺能神经元转录控制的辅助因子：对帕金森病神经元恢复能力的影响。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-06-20 DOI: 10.1080/15548627.2023.2221958

Natalia Jiménez-Moreno, Jon D Lane

{"title":"ATG8 proteins are co-factors for human dopaminergic neuronal transcriptional control: implications for neuronal resilience in Parkinson disease.","authors":"Natalia Jiménez-Moreno, Jon D Lane","doi":"10.1080/15548627.2023.2221958","DOIUrl":"10.1080/15548627.2023.2221958","url":null,"abstract":"Parkinson disease (PD) is caused by the loss of ventral midbrain dopaminergic neurons (mDANs) in the substantia nigra pars compacta (SNpc). These cells are especially vulnerable to stress but can be protected by autophagy enhancement strategies in vitro and in vivo. In our recent study, we focused on the LIM (Lin11, Isl-1, and Mec-3)-domain homeobox transcription factors LMX1A (LIM homeobox transcription factor 1 alpha) and LMX1B (LIM homeobox transcription factor 1 beta), crucial drivers of mDAN differentiation with roles in autophagy gene expression for stress protection in the developed brain. Using human induced pluripotent stem cell (hiPSC)-derived mDANs and transformed human cell lines, we found that these autophagy gene transcription factors are themselves regulated by autophagy-mediated turnover. LMX1B possesses a non-canonical LC3-interacting region (LIR) in its C-terminus through which it interacts with ATG8 family members. The LMX1B LIR-like domain enables binding to ATG8 proteins in the nucleus, where ATG8 proteins act as co-factors for robust transcription of LMX1B target genes. Thus, we propose a novel role for ATG8 proteins as autophagy gene transcriptional co-factors for mDAN stress protection in PD.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"955-957"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9668942","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}

引用次数: 0

The nonautophagic functions of autophagy-related proteins. 自噬相关蛋白的非自噬功能。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-09-08 DOI: 10.1080/15548627.2023.2254664

Jia-Ni Shang, Chen-Ge Yu, Rui Li, Yan Xi, Yue Jenny Jian, Nan Xu, Su Chen

引用次数: 0

Tracking the transition from an ATG9A vesicle to an autophagosome. 跟踪从 ATG9A 囊泡到自噬体的转变。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-07-26 DOI: 10.1080/15548627.2023.2232641

David Broadbent, Carlo Barnaba, Jens C Schmidt

引用次数: 0

Autophagy is required for stem-cell-mediated endometrial programming and the establishment of pregnancy. 干细胞介导的子宫内膜编程和妊娠的建立都需要自噬作用。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-07-05 DOI: 10.1080/15548627.2023.2231270

Pooja Popli, Ramakrishna Kommagani

引用次数: 0

ATG16L1 is equipped with two distinct WIPI2-binding sites to drive autophagy. ATG16L1 具有两个不同的 WIPI2 结合位点，可驱动自噬。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-05-14 DOI: 10.1080/15548627.2023.2213038

Xinyu Gong, Lifeng Pan

{"title":"ATG16L1 is equipped with two distinct WIPI2-binding sites to drive autophagy.","authors":"Xinyu Gong, Lifeng Pan","doi":"10.1080/15548627.2023.2213038","DOIUrl":"10.1080/15548627.2023.2213038","url":null,"abstract":"The recruitment of ATG12-ATG5-ATG16L1 complex to phagophore mediated by the specific interaction between ATG16L1 and WIPI2, is pivotal to the formation of autophagosomes during macroautophagy. Recently, we reported that ATG16L1 contains two distinct WIPI2-binding sites, the previously reported WIPI2-binding site (WBS1), and the newly identified site (WBS2). By determining the crystal structures of WIPI2 with ATG16L1 WBS1 and WBS2 respectively, we uncovered that, unlike ATG16L1 WBS1, ATG16L1 WBS2 and its binding mechanism to WIPI2 are conserved from yeast to mammals. Using cell-based functional assays, we further demonstrated that the integrity of two WIPI2-binding sites of ATG16L1 is essential for normal autophagic flux. In summary, our study provided mechanistic insights into the interaction of two key autophagic proteins, ATG16L1 and WIPI2, and revealed a dual-binding-site mode adopted by ATG16L1 to associate with WIPI2.Abbreviations: ATG: autophagy-related protein; CCD: coiled-coil domain; ITC: isothermal titration calorimetry; PI3KC3-C1: class III phosphatidylinositol 3-kinase complex I; PtdIns3P: phosphatidylinositol-3-phosphate; ULK: Unc-51-like kinase; WBS: WIPI2-binding site; WIPI: WD repeat domain phosphoinositide-interacting protein.","PeriodicalId":8722,"journal":{"name":"Autophagy","volume":" ","pages":"938-940"},"PeriodicalIF":14.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9454181","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}

引用次数: 0

Mycobacterium tuberculosis induces host autophagic ferritin degradation for enhanced iron bioavailability and bacterial growth. 结核分枝杆菌诱导宿主自噬铁蛋白降解，以提高铁的生物利用率和细菌生长。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-05-17 DOI: 10.1080/15548627.2023.2213983

Youchao Dai, Chuanzhi Zhu, Wei Xiao, Xinchun Chen, Yi Cai

引用次数: 0

The autophagy-related protein ATG5 is a central mediator of a non-canonical autophagy pathway hijacked by HIV-1 to weaken the host's response to infection. 自噬相关蛋白ATG5是被HIV-1劫持的非经典自噬途径的核心介质，可削弱宿主对感染的反应。

IF 14.6 1区生物学

Autophagy Pub Date : 2024-04-01 Epub Date: 2023-07-09 DOI: 10.1080/15548627.2023.2232225

Delphine Judith, Clarisse Berlioz-Torrent

引用次数: 0

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