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| 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 AccessMapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation
Autophagy is known to impact CD4+ T cell proliferation but the identity of autophagosomal components remain unclear. Here the authors leverage a transgenic mouse model to assess the autophagosomal compartment and identify interleukin-7 receptor-α as a key cargo in proliferating CD4+ T cells.
- Dingxi Zhou
- , Mariana Borsa
- & Anna Katharina Simon
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Article
| Open AccessOxygen-sensitive methylation of ULK1 is required for hypoxia-induced autophagy
Hypoxia induces mitochondrial clearance and autophagy, although the upstream mechanisms are not well defined. Here, the authors identify that oxygen-sensitive methylation of the key autophagy regulator ULK1 promotes ULK1 activation and subsequent autophagosome formation and mitochondrial clearance.
- Jingyi Li
- , Tao Zhang
- & Rui Liu
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Article
| Open AccessSpatial control of avidity regulates initiation and progression of selective autophagy
The molecular principles governing the initiation of autophagosome formation are not clearly understood. Here we show that the vacuolar protein Vac8 coordinates this process by promoting an avidity-driven assembly of several autophagy factors.
- David M. Hollenstein
- , Mariya Licheva
- & Claudine Kraft
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Article
| Open AccessRIPK1 regulates starvation resistance by modulating aspartate catabolism
RIPK1 is critical for normal development and cell death. Here, the authors identify a metabolic role for RIPK1 in aspartate homeostasis, as increased aspartate levels in RIPK1-deficient cells inhibits starvation-induced autophagy by ULK1.
- Xinyu Mei
- , Yuan Guo
- & Zheng-Jiang Zhu
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Article
| Open AccessLong-term autophagy is sustained by activation of CCTβ3 on lipid droplets
The source of phospholipids to generate autophagosomal membranes, particularly after prolonged starvation, is not well characterized. Here, the authors show that CCTβ3, the rate limiting enzyme in phosphatidylcholine synthesis, is activated on lipid droplets and sustains long-term autophagy.
- Yuta Ogasawara
- , Jinglei Cheng
- & Toyoshi Fujimoto
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Article
| Open AccessInhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy
Autosomal dominant optic atrophy is caused by mutations in the mitochondrial fusion protein OPA1. Here, the authors show that AMPK-induced autophagy depletes mitochondria in axons of retinal ganglion cells and that autophagic inhibition reverses vision loss in a mouse model.
- Marta Zaninello
- , Konstantinos Palikaras
- & Luca Scorrano
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| Open AccessImpaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency
Methylmalonic acidemia is an inherited metabolic disease caused by loss or mutation of the enzyme MMUT. Here the authors use cell and animal models to show that MMUT mutations lead to defective mitophagy and stress in kidney cells, contributing to the pathogenesis in methylmalonic acidemia patients.
- Alessandro Luciani
- , Anke Schumann
- & Olivier Devuyst
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| Open AccessThe inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection
The influenza virus hemagglutinin (HA) protein is a target for antivirals. Here, using a multivalent peptide library screen, the authors identify PVF-tet as an HA inhibitor and show that the peptide inhibits IAV replication by sequestering HA into amphisomes, suggesting these to represent a type of anti-viral machinery.
- Jumpei Omi
- , Miho Watanabe-Takahashi
- & Kiyotaka Nishikawa
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| Open AccessPlant AtEH/Pan1 proteins drive autophagosome formation at ER-PM contact sites with actin and endocytic machinery
Arabidopsis EH/Pan1 proteins are part of the TPLATE complex (TPC) that is required for endocytosis in plants. Here, the authors show AtEH/Pan1 proteins also act in actin-mediated autophagy, by interacting with VAP27-1 at ER-PM contact sites and recruiting TPLATE and AP-2 complex subunits, clathrin and ARP2/3/ proteins to autophagosomes.
- Pengwei Wang
- , Roman Pleskot
- & Patrick J. Hussey
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Article
| Open AccessOmegasome-proximal PtdIns(4,5)P2 couples F-actin mediated mitoaggregate disassembly with autophagosome formation during mitophagy
Autophagic cells coordinate substrate remodeling with sequestration during autophagosome formation. Here, the authors show that during Parkin-mediated mitophagy, mitochondria are disassembled into progressively smaller aggregates near autophagy initiation sites in a PtdIns(4,5)P2-dependent manner.
- Cheng-Wei Hsieh
- & Wei Yuan Yang
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Article
| Open AccessLC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy
Selective autophagy receptors are thought to selectively recruit Atg8 positive membranes to cargo via their LIR motif. Here, the authors show the LIR motifs in OPTN and NDP52 are dispensable for selectivity, functioning instead to recruit additional receptors and amplify mitophagy.
- Benjamin Scott Padman
- , Thanh Ngoc Nguyen
- & Michael Lazarou
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Article
| Open AccessCholesterol and ORP1L-mediated ER contact sites control autophagosome transport and fusion with the endocytic pathway
Autophagy requires transport of autophagosomes to the perinuclear region. Here, the authors show that ORP1L localizes to autophagosomes and mediates formation of ER contact sites that prevent autophagosome transport and fusion with endocytic vesicles when cholesterol levels are low.
- Ruud H. Wijdeven
- , Hans Janssen
- & Jacques Neefjes
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| Open AccessActin nucleation by WH2 domains at the autophagosome
Autophagy is a catabolic process whereby cellular components are degraded by the autophagosome, but the role of the actin cytoskeleton is not clear. Here Coutts and La Thangue show that the actin nucleator JMY is recruited to the autophagosome via binding LC3, and promotes actin nucleation that is required for autophagosome maturation.
- Amanda S. Coutts
- & Nicholas B. La Thangue
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Article
| Open AccessAcetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth
Beclin 1 is an essential autophagy effector, necessary to form the autophagosome. Here Sun et al. show that Beclin 1 acetylation regulated by p300 and SIRT1 inhibits autophagosome maturation, and mutation of the acetylation sites leads to tumour growth suppression in vivo.
- Ting Sun
- , Xuan Li
- & Xiao-Feng Zhu
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Article
| Open AccessAutophagosome–lysosome fusion is independent of V-ATPase-mediated acidification
BafilomycinA1 is an autophagy inhibitor, presumably owing to its blocking effect on the lysosomal proton pump V-ATPase. Here the authors show that V-ATPase-deficient lysosomes can still fuse with autophagosomes, showing that lysosomal acidification and fusion are two separable, independent events.
- Caroline Mauvezin
- , Péter Nagy
- & Thomas P. Neufeld
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| Open AccessClusterin facilitates stress-induced lipidation of LC3 and autophagosome biogenesis to enhance cancer cell survival
The induction of autophagy under stress conditions such as chemotherapy is a contributing factor towards resistance to anticancer therapy. Here, Zhang et al. identify the molecular chaperone clusterin as an adaptor that facilitates lipidation of LC3 and autophagosome biogenesis.
- Fan Zhang
- , Masafumi Kumano
- & Martin E. Gleave
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ATG5 defines a phagophore domain connected to the endoplasmic reticulum during autophagosome formation in plants
Compared with yeast and animal cells, the detailed dynamics of autophagosome extension in plants remain particularly unclear. Here the authors show that the autophagy-related protein, ATG5, forms a torus-shaped domain on the early phagophore in Arabidopsis, and involve the ER in a model for plant autophagosome formation.
- Romain Le Bars
- , Jessica Marion
- & Michele Wolfe Bianchi
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Yeast and mammalian autophagosomes exhibit distinct phosphatidylinositol 3-phosphate asymmetries
The core mechanisms of autophagy are generally assumed to be broadly conserved between yeast and mammals. Cheng et al. show that the distribution of PtdIns(3)P between cytoplasmic and luminal leaflets of autophagosomes differs dramatically in yeast and mammalian cells, suggestive of different underlying mechanisms.
- Jinglei Cheng
- , Akikazu Fujita
- & Toyoshi Fujimoto
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The phospholipase D1 pathway modulates macroautophagy
Macroautophagy involves remodelling of intracellular membranes, but the role of lipids and lipid enzymes in this process is poorly understood. Here, the authors demonstrate that phospholipase D1, an enzyme that catalyses the production of phosphatidic acid, has a modulatory role in the autophagy process in mammalian cells.
- Claudia Dall'Armi
- , Andrés Hurtado-Lorenzo
- & Gilbert Di Paolo