CoChat
Sign Up
Cited by 36

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

ADAM17‐triggered TNF signalling protects the ageing Drosophila retina from lipid droplet‐mediated degeneration

Muliyil, Sonia, Levet, Clémence, Düsterhöft, Stefan, Dulloo, Iqbal, Cowley, Sally A, Freeman, Matthew·2020·The EMBO Journal
DOI 10.15252/embj.2020104415PMC PMC7459420

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Animals have evolved multiple mechanisms to protect themselves from the cumulative effects of age‐related cellular damage. Here, we reveal an unexpected link between the TNF (tumour necrosis factor) inflammatory pathway, triggered by the metalloprotease ADAM17/TACE, and a lipid droplet (LD)‐mediated mechanism of protecting retinal cells from age‐related degeneration. Loss of ADAM17, TNF and the TNF receptor Grindelwald in pigmented glial cells of the Drosophila retina leads to age‐related degeneration of both glia and neurons, preceded by an abnormal accumulation of glial LDs. We show that the glial LDs initially buffer the cells against damage caused by glial and neuronally generated reactive oxygen species (ROS), but that in later life the LDs dissipate, leading to the release of toxic peroxidated lipids. Finally, we demonstrate the existence of a conserved pathway in human iPS‐derived microglia‐like cells, which are central players in neurodegeneration. Overall, we have discovered a pathway mediated by TNF signalling acting not as a trigger of inflammation, but as a cytoprotective factor in the retina.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.15252/embj.2020104415

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 68

  1. Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double‐edged sword. Nat Rev Immunol 3: 745–756 · DOI · Paper page
  2. Agrawal N, Delanoue R, Mauri A, Basco D, Pasco M, Thorens B, Leopold P (2016) The Drosophila TNF eiger is an adipokine that acts on insulin‐producing cells to mediate nutrient response. Cell Metab 23: 675–684 · DOI
  3. Amer J, Atlas D, Fibach E (2008) N‐acetylcysteine amide (AD4) attenuates oxidative stress in beta‐thalassemia blood cells. Biochim Biophys Acta 1780: 249–255 · DOI
  4. Andersen DS, Colombani J, Palmerini V, Chakrabandhu K, Boone E, Rothlisberger M, Toggweiler J, Basler K, Mapelli M, Hueber AO et al (2015) The Drosophila TNF receptor Grindelwald couples loss of cell polarity and neoplastic growth. Nature 522: 482–486 · DOI
  5. Arribas J, Esselens C (2009) ADAM17 as a therapeutic target in multiple diseases. Curr Pharm Des 15: 2319–2335 · DOI
  6. Bailey AP, Koster G, Guillermier C, Hirst EM, MacRae JI, Lechene CP, Postle AD, Gould AP (2015) Antioxidant role for lipid droplets in a stem cell niche of Drosophila. Cell 163: 340–353 · DOI
  7. Bastos RG, Howard ZP, Hiroyasu A, Goodman AG (2017) Host and bacterial factors control susceptibility of Drosophila melanogaster to Coxiella burnetii Infection. Infect Immun 85: e00218‐17 · DOI
  8. Baumgart A, Seidl S, Vlachou P, Michel L, Mitova N, Schatz N, Specht K, Koch I, Schuster T, Grundler R et al (2010) ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non‐small cell lung cancer. Cancer Res 70: 5368–5378 · DOI
  9. Bensaad K, Favaro E, Lewis CA, Peck B, Lord S, Collins JM, Pinnick KE, Wigfield S, Buffa FM, Li JL et al (2014) Fatty acid uptake and lipid storage induced by HIF‐1alpha contribute to cell growth and survival after hypoxia‐reoxygenation. Cell Rep 9: 349–365 · DOI
  10. Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S et al (1997) A metalloproteinase disintegrin that releases tumour‐necrosis factor‐alpha from cells. Nature 385: 729–733 · DOI · Paper page
  11. Boulant S, Douglas MW, Moody L, Budkowska A, Targett‐Adams P, McLauchlan J (2008) Hepatitis C virus core protein induces lipid droplet redistribution in a microtubule‐ and dynein‐dependent manner. Traffic 9: 1268–1282 · DOI
  12. Boutet P, Aguera‐Gonzalez S, Atkinson S, Pennington CJ, Edwards DR, Murphy G, Reyburn HT, Vales‐Gomez M (2009) Cutting edge: the metalloproteinase ADAM17/TNF‐alpha‐converting enzyme regulates proteolytic shedding of the MHC class I‐related chain B protein. J Immunol 182: 49–53 · DOI
  13. Bradley JR (2008) TNF‐mediated inflammatory disease. J Pathol 214: 149–160 · DOI · Paper page
  14. Bravo R, Parra V, Gatica D, Rodriguez AE, Torrealba N, Paredes F, Wang ZV, Zorzano A, Hill JA, Jaimovich E et al (2013) Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration. Int Rev Cell Mol Biol 301: 215–290 · DOI
  15. Chalaris A, Adam N, Sina C, Rosenstiel P, Lehmann‐Koch J, Schirmacher P, Hartmann D, Cichy J, Gavrilova O, Schreiber S et al (2010) Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice. J Exp Med 207: 1617–1624 · DOI
  16. Chen X, Hall H, Simpson JP, Leon‐Salas WD, Ready DF, Weake VM (2017) Cytochrome b5 protects photoreceptors from light stress‐induced lipid peroxidation and retinal degeneration. NPJ Aging Mech Dis 3: 18 · DOI
  17. Chen T, Zhu J, Wang YH, Hang CH (2019) ROS‐mediated mitochondrial dysfunction and ER stress contribute to compression‐induced neuronal injury. Neuroscience 416: 268–280 · DOI
  18. Cheung W, Gill M, Esposito A, Kaminski CF, Courousse N, Chwetzoff S, Trugnan G, Keshavan N, Lever A, Desselberger U (2010) Rotaviruses associate with cellular lipid droplet components to replicate in viroplasms, and compounds disrupting or blocking lipid droplets inhibit viroplasm formation and viral replication. J Virol 84: 6782–6798 · DOI
  19. Dafinca R, Scaber J, Ababneh N, Lalic T, Weir G, Christian H, Vowles J, Douglas AG, Fletcher‐Jones A, Browne C et al (2016) C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis and stress granule formation in induced pluripotent stem cell‐derived neurons from patients with amyotrophic lateral sclerosis and frontotemporal dementia. Stem Cells 34: 2063–2078 · DOI
  20. Dang M, Armbruster N, Miller MA, Cermeno E, Hartmann M, Bell GW, Root DE, Lauffenburger DA, Lodish HF, Herrlich A (2013) Regulated ADAM17‐dependent EGF family ligand release by substrate‐selecting signaling pathways. Proc Natl Acad Sci USA 110: 9776–9781 · DOI
  21. Davalli P, Mitic T, Caporali A, Lauriola A, D'Arca D (2016) ROS, cell senescence, and novel molecular mechanisms in aging and age‐related diseases. Oxid Med Cell Longev 2016: 3565127 · DOI · Paper page
  22. Edwards TN, Meinertzhagen IA (2010) The functional organisation of glia in the adult brain of Drosophila and other insects. Prog Neurobiol 90: 471–497 · DOI
  23. Fernandes HJ, Hartfield EM, Christian HC, Emmanoulidou E, Zheng Y, Booth H, Bogetofte H, Lang C, Ryan BJ, Sardi SP et al (2016) ER stress and autophagic perturbations lead to elevated extracellular alpha‐Synuclein in GBA‐N370S Parkinson's iPSC‐derived dopamine neurons. Stem Cell Reports 6: 342–356 · DOI
  24. Ferrucci L, Fabbri E (2018) Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol 15: 505–522 · DOI · Paper page
  25. Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A (2018) Inflammaging: a new immune‐metabolic viewpoint for age‐related diseases. Nat Rev Endocrinol 14: 576–590 · DOI · Paper page
  26. Gaschler MM, Stockwell BR (2017) Lipid peroxidation in cell death. Biochem Biophys Res Commun 482: 419–425 · DOI
  27. Igaki T, Kanda H, Yamamoto‐Goto Y, Kanuka H, Kuranaga E, Aigaki T, Miura M (2002) Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J 21: 3009–3018 · DOI
  28. Kanda H, Igaki T, Kanuka H, Yagi T, Miura M (2002) Wengen, a member of the Drosophila tumor necrosis factor receptor superfamily, is required for Eiger signaling. J Biol Chem 277: 28372–28375 · DOI
  29. Karran E, De Strooper B (2016) The amyloid cascade hypothesis: are we poised for success or failure? J Neurochem 139(Suppl 2): 237–252 · DOI · Paper page
  30. Kauppila S, Maaty WS, Chen P, Tomar RS, Eby MT, Chapo J, Chew S, Rathore N, Zachariah S, Sinha SK et al (2003) Eiger and its receptor, Wengen, comprise a TNF‐like system in Drosophila. Oncogene 22: 4860–4867 · DOI
  31. Ketteler R, Glaser S, Sandra O, Martens UM, Klingmuller U (2002) Enhanced transgene expression in primitive hematopoietic progenitor cells and embryonic stem cells efficiently transduced by optimized retroviral hybrid vectors. Gene Ther 9: 477–487 · DOI
  32. Kirby K, Hu J, Hilliker AJ, Phillips JP (2002) RNA interference‐mediated silencing of Sod2 in Drosophila leads to early adult‐onset mortality and elevated endogenous oxidative stress. Proc Natl Acad Sci USA 99: 16162–16167 · DOI
  33. Klaips CL, Jayaraj GG, Hartl FU (2018) Pathways of cellular proteostasis in aging and disease. J Cell Biol 217: 51–63 · DOI
  34. Layerenza JP, Gonzalez P, Garcia de Bravo MM, Polo MP, Sisti MS, Ves‐Losada A (2013) Nuclear lipid droplets: a novel nuclear domain. Biochim Biophys Acta 1831: 327–340 · DOI
  35. Li Z, Johnson MR, Ke Z, Chen L, Welte MA (2014) Drosophila lipid droplets buffer the H2Av supply to protect early embryonic development. Curr Biol 24: 1485–1491 · DOI
  36. Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A et al (2015) Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell 160: 177–190 · DOI · Paper page
  37. Liu L, MacKenzie KR, Putluri N, Maletic‐Savatic M, Bellen HJ (2017) The Glia‐neuron lactate shuttle and elevated ROS promote lipid synthesis in neurons and lipid droplet accumulation in Glia via APOE/D. Cell Metab 26: 719–737 e716 · DOI · Paper page
  38. Lorenzen I, Lokau J, Korpys Y, Oldefest M, Flynn CM, Kunzel U, Garbers C, Freeman M, Grotzinger J, Dusterhoft S (2016) Control of ADAM17 activity by regulation of its cellular localisation. Sci Rep 6: 35067 · DOI
  39. Moller‐Hackbarth K, Dewitz C, Schweigert O, Trad A, Garbers C, Rose‐John S, Scheller J (2013) A disintegrin and metalloprotease (ADAM) 10 and ADAM17 are major sheddases of T cell immunoglobulin and mucin domain 3 (Tim‐3). J Biol Chem 288: 34529–34544 · DOI
  40. Morante J, Desplan C (2005) Photoreceptor axons play hide and seek. Nat Neurosci 8: 401–402 · DOI
  41. Mustafi R, Dougherty U, Mustafi D, Ayaloglu‐Butun F, Fletcher M, Adhikari S, Sadiq F, Meckel K, Haider HI, Khalil A et al (2017) ADAM17 is a tumor promoter and therapeutic target in western diet‐associated colon cancer. Clin Cancer Res 23: 549–561 · DOI
  42. Narasimamurthy R, Geuking P, Ingold K, Willen L, Schneider P, Basler K (2009) Structure‐function analysis of Eiger, the Drosophila TNF homolog. Cell Res 19: 392–394 · DOI
  43. Niki E (2009) Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med 47: 469–484 · DOI
  44. Olzmann JA, Carvalho P (2019) Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol 20: 137–155 · DOI · Paper page
  45. O'Neil SM, Witcher KG, McKim DB, Godbout JP (2018) Forced turnover of aged microglia induces an intermediate phenotype but does not rebalance CNS environmental cues driving priming to immune challenge. Acta Neuropathol Commun 6: 129 · DOI
  46. Postlethwaite AE, Seyer JM (1990) Stimulation of fibroblast chemotaxis by human recombinant tumor necrosis factor alpha (TNF‐alpha) and a synthetic TNF‐alpha 31‐68 peptide. J Exp Med 172: 1749–1756 · DOI
  47. Puls A, Eliopoulos AG, Nobes CD, Bridges T, Young LS, Hall A (1999) Activation of the small GTPase Cdc42 by the inflammatory cytokines TNF(alpha) and IL‐1, and by the Epstein‐Barr virus transforming protein LMP1. J Cell Sci 112(Pt 17): 2983–2992 · DOI
  48. Qi H, Rand MD, Wu X, Sestan N, Wang W, Rakic P, Xu T, Artavanis‐Tsakonas S (1999) Processing of the notch ligand delta by the metalloprotease Kuzbanian. Science 283: 91–94 · DOI
  49. Sahin U, Weskamp G, Kelly K, Zhou HM, Higashiyama S, Peschon J, Hartmann D, Saftig P, Blobel CP (2004) Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol 164: 769–779 · DOI
  50. Sandoval H, Yao CK, Chen K, Jaiswal M, Donti T, Lin YQ, Bayat V, Xiong B, Zhang K, David G et al (2014) Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production. Elife 3: 25313867 · DOI
  51. Schimel AM, Abraham L, Cox D, Sene A, Kraus C, Dace DS, Ercal N, Apte RS (2011) N‐acetylcysteine amide (NACA) prevents retinal degeneration by up‐regulating reduced glutathione production and reversing lipid peroxidation. Am J Pathol 178: 2032–2043 · DOI
  52. Schuldiner M, Bohnert M (2017) A different kind of love – lipid droplet contact sites. Biochim Biophys Acta Mol Cell Biol Lipids 1862: 1188–1196 · DOI
  53. Sedger LM, McDermott MF (2014) TNF and TNF‐receptors: from mediators of cell death and inflammation to therapeutic giants – past, present and future. Cytokine Growth Factor Rev 25: 453–472 · DOI
  54. Shanmugam G, Narasimhan M, Sakthivel R, Kumar RR, Davidson C, Palaniappan S, Claycomb WW, Hoidal JR, Darley‐Usmar VM, Rajasekaran NS (2016) A biphasic effect of TNF‐alpha in regulation of the Keap1/Nrf2 pathway in cardiomyocytes. Redox Biol 9: 77–89 · DOI
  55. Shen HM, Liu ZG (2006) JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med 40: 928–939 · DOI · Paper page
  56. Shinozaki Y, Nomura M, Iwatsuki K, Moriyama Y, Gachet C, Koizumi S (2014) Microglia trigger astrocyte‐mediated neuroprotection via purinergic gliotransmission. Sci Rep 4: 4329 · DOI
  57. Soltysik K, Ohsaki Y, Tatematsu T, Cheng J, Fujimoto T (2019) Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis. Nat Commun 10: 473 · DOI · Paper page
  58. Squier TC (2001) Oxidative stress and protein aggregation during biological aging. Exp Gerontol 36: 1539–1550 · DOI
  59. Thiam AR, Dugail I (2019) Lipid droplet‐membrane contact sites – from protein binding to function. J Cell Sci 132: jcs230169 · DOI
  60. Uzbekov R, Roingeard P (2013) Nuclear lipid droplets identified by electron microscopy of serial sections. BMC Res Notes 6: 386 · DOI
  61. Van Den Brink DM, Cubizolle A, Chatelain G, Davoust N, Girard V, Johansen S, Napoletano F, Dourlen P, Guillou L, Angebault‐Prouteau C et al (2018) Physiological and pathological roles of FATP‐mediated lipid droplets in Drosophila and mice retina. PLoS Genet 14: e1007627 · DOI · Paper page
  62. Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10: 45–65 · DOI
  63. Wallach D, Arumugam TU, Boldin MP, Cantarella G, Ganesh KA, Goltsev Y, Goncharov TM, Kovalenko AV, Rajput A, Varfolomeev EE et al (2002) How are the regulators regulated? The search for mechanisms that impose specificity on induction of cell death and NF‐kappaB activation by members of the TNF/NGF receptor family. Arthritis Res 4(Suppl 3): S189–196 · DOI
  64. Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334: 1081–1086 · DOI
  65. Wellen KE, Thompson CB (2010) Cellular metabolic stress: considering how cells respond to nutrient excess. Mol Cell 40: 323–332 · DOI · Paper page
  66. Welte MA, Cermelli S, Griner J, Viera A, Guo Y, Kim DH, Gindhart JG, Gross SP (2005) Regulation of lipid‐droplet transport by the perilipin homolog LSD2. Curr Biol 15: 1266–1275 · DOI
  67. Welte MA, Gould AP (2017) Lipid droplet functions beyond energy storage. Biochim Biophys Acta Mol Cell Biol Lipids 1862: 1260–1272 · DOI
  68. Zunke F, Rose‐John S (2017) The shedding protease ADAM17: physiology and pathophysiology. Biochim Biophys Acta Mol Cell Res 1864: 2059–2070 · DOI

Cited by

Sorted by citations

Metadata

Authors
Muliyil, S., Levet, C., Düsterhöft, S., Dulloo, I., Cowley, S. A., & Freeman, M.
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2020-07-26
Volume
39
Issue
17
ISSN
  • 0261-4189
  • 1460-2075
DOI
10.15252/embj.2020104415
PMC
PMC7459420
Cited by
36
References
7
Language
en
Licence
Funders
  • Wellcome Trust (101035/Z/13/Z)
  • Human Frontier Science Program
  • European Molecular Biology Organization
  • Deutsche Forschungsgemeinschaft (DU 1582/1-1)
  • UK Research and Innovation | Medical Research Council (MC_EX_MR/N50192X/1)
  • Parkinson's UK (J-1403)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review