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| Open AccessAutophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation
A seed consists of an embryo, endosperm, and seed coat. Here the authors show that autophagy plays a crucial role in regulating timely programmed cell death in the innermost seed coat, thereby influencing embryo pattern formation and seed viability.
- Lin-lin Zhao
- , Ru Chen
- & Peng Zhao
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Article
| Open AccessSKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration
Secretory autophagy (SA) plays a crucial role in neuroinflammation-driven neurodegeneration, through SKA2 and FKBP5. SKA2 regulation of SA can inhibit IL-1β release. Its dysfunction leads to neurodegeneration, and is linked to Alzheimer’s disease.
- Jakob Hartmann
- , Thomas Bajaj
- & Nils C. Gassen
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Article
| Open AccessAutophagy regulates the maturation of hematopoietic precursors in the embryo
The production of hematopoietic stem cells in the embryo is precisely regulated by various intrinsic and extrinsic factors. Here, the authors find that autophagy is involved in the maturation of hematopoietic precursors through nucleolin pathways.
- Yumin Liu
- , Linjuan Shi
- & Zhuan Li
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Article
| Open AccessNME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia
NME3 is a member of NDPK family. Here, Chen et. al., discover that histidine phosphorylatable NME3 is required for hypoxia-induced mitophagy via PA-dependent interaction with Drp1, which is protected from MUL1-mediated ubiquitination for mitophagy.
- Chih-Wei Chen
- , Chi Su
- & Zee-Fen Chang
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| Open AccessTheileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy
Theileria parasites have evolved mechanisms to evade host cell defenses. Here, Villares et al use an anti-parasite drug to show how intracellular parasites sequester host eIF5A to escape elimination by autophagy pathways.
- Marie Villares
- , Nelly Lourenço
- & Jonathan B. Weitzman
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Article
| Open AccessPsAF5 functions as an essential adapter for PsPHB2-mediated mitophagy under ROS stress in Phytophthora sojae
ROS is an important defense means against pathogens for host. Here the authors show that PsAF5 functions as a mitophagy adapter and regulates mitochondrial homeostasis in Phytophthora sojae under ROS stress, which is crucial for its infection.
- Wenhao Li
- , Hongwei Zhu
- & Xili Liu
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Article
| Open AccessAttenuation of phytofungal pathogenicity of Ascomycota by autophagy modulators
Woo et al. report new autophagy inhibitors identified through a high-throughput chemical screening using a BRET-based assay and an ATG8 synthetic sensor, that function as safe and effective fungicides against broad fungal pathogens.
- Jongchan Woo
- , Seungmee Jung
- & Savithramma P. Dinesh-Kumar
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Article
| Open AccessALLO-1- and IKKE-1-dependent positive feedback mechanism promotes the initiation of paternal mitochondrial autophagy
Allophagy eliminates paternal mitochondria in C. elegans embryos. This study reveals that an autophagy adaptor, ALLO-1, recognizes cargos and initiates autophagosome formation by gathering with the ULK complex in an IKKE-1 kinase-dependent manner.
- Taeko Sasaki
- , Yasuharu Kushida
- & Miyuki Sato
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Article
| Open AccessNutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control
The quality of germline mitochondria is essential for producing healthy oocytes. Here, Ng, Chan and Pek report a stable intron that modulates germline mitochondrial quality control during fasting, heat stress and aging.
- Annabel Qi En Ng
- , Seow Neng Chan
- & Jun Wei Pek
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Article
| Open AccessRelaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status
Restoring mitochondrial function has emerged as a promising therapeutic strategy for diabetic retinopathy. Here, the authors show that mitochondrial hyperfusion blunts mitophagy during the disease process, and that rescuing this process pharmacologically confers retinal neuroprotection independent of an improved glycaemic status in type-1 diabetic mice.
- Aidan Anderson
- , Nada Alfahad
- & Jose R. Hombrebueno
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Article
| Open AccessMitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity
Stress-independent autophagy is less understood than stress-induced autophagy and is important for thymic self-tolerance. Here the authors show that a mitochondrial protein C15ORF48 is important for stress-independent autophagy and alters glutathione metabolism and C15orf48 knockout mice develop autoimmunity and changes to thymic epithelial cells.
- Yuki Takakura
- , Moeka Machida
- & Noritaka Yamaguchi
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Article
| Open AccessDENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy
Small GTPases such as Rabs control the positioning of lysosomes. Here, the authors unveil a molecular cascade orchestrated by Arl8/DENND6A/Rab34 that regulates lysosome location, impacting autophagy.
- Rahul Kumar
- , Maleeha Khan
- & Peter S. McPherson
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Article
| Open AccessMolecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy
The balance between apoptosis and autophagy is critical for normal development, proper tissue function, and disease pathogenesis. Here, the authors show previously unannotated BIRC6 domains, including a ubiquitin-like domain, and how it utilizes its ubiquitylation function to regulate both apoptosis and autophagy.
- Shuo-Shuo Liu
- , Tian-Xia Jiang
- & Xiao-Bo Qiu
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Article
| Open AccessMitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging
Dysregulated autophagy and mitochondrial function are two well-described hallmarks of aging. Here, the authors describe an unexpected age-associated upregulation of mitophagy in response to neuroinflammation triggered by leaked mtDNA.
- Juan Ignacio Jiménez-Loygorri
- , Beatriz Villarejo-Zori
- & Patricia Boya
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| Open AccessATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover
Lipophagy is the degradation of lipid droplets by the autophagy machinery. Here, the authors identify that autophagy protein ATG14 also targets lipid droplets and interacts with ATG8 proteins, functioning as an autophagic receptor for STX18-regulated lipophagy.
- Zhen Yuan
- , Kun Cai
- & Binbin Ding
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Article
| Open AccessUpregulated pexophagy limits the capacity of selective autophagy
An accumulation of one substrate of selective autophagy can lead to autophagic degradation deficiencies. Here, the authors show that a pathogenic increase in a single autophagy pathway restricts another by consuming the cell’s autophagy capacity.
- Kyla Germain
- , Raphaella W. L. So
- & Peter K. Kim
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| Open AccessAngiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts
The functional heterogeneity of autophagy in endothelial cells during angiogenesis remains incompletely understood. Here, the authors apply a 3D angiogenesis-on-a-chip coupled with single-cell RNA sequencing to find distinct autophagy functions in two different endothelial cell populations during angiogenic sprouting.
- Somin Lee
- , Hyunkyung Kim
- & Noo Li Jeon
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Article
| Open AccessExperimental determination and mathematical modeling of standard shapes of forming autophagosomes
Autophagosome formation involves membrane morphological changes. Here, authors statistically determined average shapes of forming autophagosomes from 3D electron micrographs and established a theoretical model that quantitatively reproduces them.
- Yuji Sakai
- , Satoru Takahashi
- & Noboru Mizushima
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Article
| Open AccessTMEM55B links autophagy flux, lysosomal repair, and TFE3 activation in response to oxidative stress
Lysosomes are critical regulators of cellular homeostasis. Here, the authors report that the lysosomal protein TMEM55B orchestrates cellular response to acute oxidative stress by coordinating autophagosome degradation, lysosomal repair, and activation of transcriptional stress responses.
- Eutteum Jeong
- , Rose Willett
- & Rosa Puertollano
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Article
| Open AccessNEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62
Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62.
- Nikolas Furthmann
- , Verian Bader
- & Konstanze F. Winklhofer
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| Open AccessAutophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury
Understanding the role of GPX4 in cell ferroptosis at the interface of the inner cortex and medulla is crucial in the context of renal injury. Here, the authors demonstrate that the OTUD5 interaction with GPX4 is key in resisting ischemia/reperfusion-induced ferroptosis in renal cells, offering a new strategy for treating acute kidney injury.
- Li-Kai Chu
- , Xu Cao
- & Jun Liu
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Article
| Open AccessThe function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways
Berkane et al. investigated the activation process of selective autophagy of the ER. They show that that phosphorylation of FAM134 proteins by CK2 is a prerequisite for the formation of large micro-clusters of high-density at the ER membrane.
- Rayene Berkane
- , Hung Ho-Xuan
- & Alexandra Stolz
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| Open AccessGRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis
Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.
- Qiang Zhu
- , Matthew E. Combs
- & Joan M. Taylor
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Article
| Open AccessExcess PrPC inhibits muscle cell differentiation via miRNA-enhanced liquid–liquid phase separation implicated in myopathy
The prion protein PrPC is known to play a role in skeletal muscle development and physiology, including in myopathy. Here, the authors report that excess PrPC binds microRNAs that enhance its aggregation, which inhibits autophagy in muscle cells.
- Jing Tao
- , Yanping Zeng
- & Yi Liang
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Article
| Open AccessAtg18 oligomer organization in assembled tubes and on lipid membrane scaffolds
In this work, the authors determined the cryo-EM structures of autophagy-related protein 18 organized in helical tubes and provide insights into the molecular framework for the positioning of downstream components of the autophagy machinery.
- Daniel Mann
- , Simon A. Fromm
- & Carsten Sachse
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Article
| Open AccessThe AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells
Urinary flow is sensed by renal cells but its intensity is dysregulated in renal diseases. Here, the authors report that physiological flow inhibits YAP to promote autophagy, while pathological flow leads to YAP activation and autophagy inhibition.
- Aurore Claude-Taupin
- , Pierre Isnard
- & Nicolas Dupont
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Article
| Open AccessLocal membrane source gathering by p62 body drives autophagosome formation
Phase separated p62 body plays pivotal roles in autophagy. Here, the authors describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation.
- Xuezhao Feng
- , Daxiao Sun
- & Na Mi
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Article
| Open AccessSpliceosome component Usp39 contributes to hepatic lipid homeostasis through the regulation of autophagy
Non-alcoholic fatty liver disease affects 25% of people worldwide. Here the authors report that spliceosome component Usp39 deletion in mice leads to spontaneous steatosis and impaired autophagy through the regulation of alternative splicing.
- Donghai Cui
- , Zixiang Wang
- & Zhaojian Liu
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Article
| Open AccessPPTC7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy
The mitochondrial phosphatase PPTC7 has previously been linked to the maintenance of mitochondrial content, but the mechanisms underlying this phenotype remain unclear. Here, the authors demonstrate that loss of Pptc7 results in metabolic defects and further suggest that PPTC7 is a regulator of receptor-mediated mitophagy.
- Natalie M. Niemi
- , Lia R. Serrano
- & David J. Pagliarini
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Article
| Open AccessC9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy
The HOPS complex mediates membrane tethering and autophagosome-lysosome fusion. Here, the authors biochemically reconstitute the mammalian HOPS in protoliposomes and propose a model of complex assembly that depends on Rab2 and Rab39A.
- Shen Zhang
- , Mindan Tong
- & Qing Zhong
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Article
| Open AccessNLRP6 potentiates PI3K/AKT signalling by promoting autophagic degradation of p85α to drive tumorigenesis
The crosstalk between innate immunity and autophagy plays a critical role in cancer. Here, the authors report that an immune receptor NLRP6 potentiates the PI3K/AKT pathway by selective degradation of p85α. The NLRP6-p85α interaction offers a potential therapeutic target for tumor treatment.
- Feng Zhi
- , Bowen Li
- & Jun Cui
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Article
| Open AccessTumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer
Patients with MMR-proficient, microsatellite stable (MSS) colorectal cancer (CRC) are highly resistant to immune-checkpoint inhibitors. Here the authors report that tumor intrinsic expression of the autophagy gene ATG16L1 is associated with resistance to anti-tumor immunity in preclinical CRC models and that elevated ATG16L1 expression predicts poor immunotherapy response in Kras-mutant CRC patients.
- Lucia Taraborrelli
- , Yasin Şenbabaoğlu
- & Aditya Murthy
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| Open AccessA mechanism that ensures non-selective cytoplasm degradation by autophagy
How membrane morphology is regulated during autophagosome formation remains elusive. Here, authors reveal a mechanism by which the forming autophagosomal membrane expands with a large opening for non-selective sequestration of the cytoplasm.
- Tetsuya Kotani
- , Yuji Sakai
- & Hitoshi Nakatogawa
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Article
| Open AccessCD44 connects autophagy decline and ageing in the vascular endothelium
Mechanisms underlying the connection between autophagy decline and vascular endothelial cell (VEC) ageing remain unclear. Here, the authors identify a key role for CD44 in controlling autophagy and ageing in VECs, and this function is conserved in nematodes.
- Lu Zhang
- , Peichang Yang
- & Shiwei Ma
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Article
| Open AccessPINK1 and Parkin regulate IP3R-mediated ER calcium release
Loss of two PD genes, PINK1 and Parkin, leads to a robust increase in ER calcium release. Here, the authors show that suppression of IP3R activity via inhibiting CISD1 is sufficient to rescue the PD-related phenotypes in PINK1 or Parkin null animal models.
- Su Jin Ham
- , Heesuk Yoo
- & Jongkyeong Chung
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Article
| Open AccessGlycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans
Activation of the glycerol shunt mimics calorie restriction, protects from glucotoxicity, and promotes healthy aging. Here, Possik et al. uncover the underlying mechanism and identify the AMPK-TFEB autophagy pathway as critical to the healthy aging phenotype.
- Elite Possik
- , Laura-Lee Klein
- & Marc Prentki
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Article
| Open AccessExo84c interacts with VAP27 to regulate exocytotic compartment degradation and stigma senescence
The exocyst complex is essential for plant development. Here the authors reveal a link between the exocyst complex and the ER network in regulating the degradation of exocytic compartments, stigma senescence and flower receptivity
- Tong Zhang
- , Yifan Li
- & Pengwei Wang
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Article
| Open AccessA conserved membrane curvature-generating protein is crucial for autophagosome formation in fission yeast
Rop1 is the single representaive of a subfamily of the membrane-curvature generating REEPs in fission yeast. Wang et al. show that Rop1 is crucial for the macroautophagy of organelles and cytosolic proteins, facilitating autophagosome formation.
- Ning Wang
- , Yoko Shibata
- & Tom A. Rapoport
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Article
| Open AccessAutophagy promotes jasmonate-mediated defense against nematodes
Autophagy plays a critical role in plant immunity. Here the authors show that in tomato, autophagy promotes defense against root-knot nematodes by promoting degradation of negative regulators of jasmonic acid signaling.
- Jinping Zou
- , Xinlin Chen
- & Jie Zhou
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Article
| Open AccessGenetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy
Previous studies suggested a role for CARD9 pathway in atherosclerosis but the underlying mechanisms remain poorly understood. Here, the authors show that the pro-atherogenic effects of Card9 deficiency are mediated by CD36-dependent defective autophagy that can be reversed by rapamycin and metformin.
- Yujiao Zhang
- , Marie Vandestienne
- & Hafid Ait-Oufella
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Article
| Open AccessLiver lipophagy ameliorates nonalcoholic steatohepatitis through extracellular lipid secretion
Nonalcoholic steatohepatitis (NASH) starts with lipid droplet accumulation in the liver that eventually causes inflammation and fibrosis. Here, authors use lipophagy activators to limit the accumulation of lipids in the liver and show that this can prevent disease progression in a mouse model of nonalcoholic steatohepatitis.
- Yoshito Minami
- , Atsushi Hoshino
- & Satoaki Matoba
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Article
| Open AccessA protein kinase coordinates cycles of autophagy and glutaminolysis in invasive hyphae of the fungus Magnaporthe oryzae within rice cells
The blast fungus Magnaporthe oryzae produces invasive hyphae in living rice cells during early infection. Here, the authors show that a fungal protein kinase promotes this biotrophic growth phase by coordinating cycles of autophagy and glutaminolysis in invasive hyphae.
- Gang Li
- , Ziwen Gong
- & Richard A. Wilson
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Article
| Open AccessATPase activity of DFCP1 controls selective autophagy
The endoplasmic reticulum protein DFCP1 is found on omegasomes implicated in autophagosome biogenesis, but its function has remained unknown. Here, Nähse et al. show that DFCP1 is an ATPase that mediates selective autophagy by promoting constriction of large omegasomes.
- Viola Nähse
- , Camilla Raiborg
- & Harald Stenmark
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Article
| Open AccessThe ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy
Sphingolipids can function as lipid signaling molecules. Here, the authors find that the endoplasmic reticulum calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating calcium homeostasis in endoplasmic reticulum.
- Shiyan Liu
- , Mutian Chen
- & Kefeng Lu
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Article
| Open AccessTMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress
Researchers reveal how the stress of the endoplasmic reticulum is transmitted to the nuclear envelope, which swells, and is brought back to physiologic shape by autophagic pathways.
- Marika K. Kucińska
- , Juliette Fedry
- & Maurizio Molinari
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Article
| Open AccessAugmented temperature fluctuation aggravates muscular atrophy through the gut microbiota
Higher diurnal temperature range in humans correlates with the prevalence of sarcopenia. Here, the authors show that fluctuated temperature exposure accelerates muscle atrophy and dampens exercise performance via altering microbiota composition in aged mice.
- Ya Liu
- , Yifan Guo
- & Yan Huang
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Article
| Open AccessThe mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes
Endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-phagy are two central degradative mechanisms in the ER. Here the authors describe the sequence of events underlying the disposition of misfolded ER proteins by ERAD and ER-phagy.
- Shuangcheng Alivia Wu
- , Chenchen Shen
- & Ling Qi
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Article
| Open AccessLC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models
Glia are housekeepers of the nervous system that eliminate neuronal debris after injury. Here, the authors show that LC3-associated phagocytosis in Drosophila glia promotes debris clearance after wing nerve injury and recovery after traumatic brain injury.
- Áron Szabó
- , Virág Vincze
- & Gábor Juhász
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Article
| Open AccessTRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation
cGAS/STING activation is linked to the induction of anti-tumor immune responses. Here the authors report a role for the deubiquitinating enzyme TRABID in regulating mitotic cell division and suppressing anti-tumor immunity, suggesting that TRABID inhibition induces micronuclei and activates cGAS/STING pathway.
- Yu-Hsuan Chen
- , Han-Hsiun Chen
- & Ruey-Hwa Chen