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Fas-apoptotic inhibitory molecule 2 localizes to the lysosome and facilitates autophagosome-lysosome fusion through the LC3 interaction region motif-dependent interaction with LC3

Title
Fas-apoptotic inhibitory molecule 2 localizes to the lysosome and facilitates autophagosome-lysosome fusion through the LC3 interaction region motif-dependent interaction with LC3
Authors
Hong, Caroline JeeyeonYeon, JihyeYeo, Bo KyoungWoo, HanwoongAn, Hyun-KyuHeo, WoojungKim, KyuhyungYu, Seong-Woon
DGIST Authors
Hong, Caroline Jeeyeon; Yeon, Jihye; Yeo, Bo Kyoung; Woo, Hanwoong; An, Hyun-Kyu; Heo, Woojung; Kim, KyuhyungYu, Seong-Woon
Issue Date
2020-01
Citation
FASEB Journal, 34(1), 161-179
Type
Article
Article Type
Article
Author Keywords
autolysosomeautophagosome maturationFAIM2LIRMAP1LC3Bxbx-6
Keywords
PROTEINACIDIFICATIONDEGRADATIONATPASEMODULATIONMATURATIONSYNTHASEGENESFAIM2TMBIM
ISSN
0892-6638
Abstract
Fas-apoptotic inhibitory molecule 2 (FAIM2) is a member of the transmembrane BAX inhibitor motif-containing (TMBIM) family. TMBIM family is comprised of six anti-apoptotic proteins that suppress cell death by regulating endoplasmic reticulum Ca2+ homeostasis. Recent studies have implicated two TMBIM proteins, GRINA and BAX Inhibitor-1, in mediating cytoprotection via autophagy. However, whether FAIM2 plays a role in autophagy has been unknown. Here we show that FAIM2 localizes to the lysosomes at basal state and facilitates autophagy through interaction with microtubule-associated protein 1 light chain 3 proteins in human neuroblastoma SH-SY5Y cells. FAIM2 overexpression increased autophagy flux, while autophagy flux was impaired in shRNA-mediated knockdown (shFAIM2) cells, and the impairment was more evident in the presence of rapamycin. In shFAIM2 cells, autophagosome maturation through fusion with lysosomes was impaired, leading to accumulation of autophagosomes. A functional LC3-interacting region motif within FAIM2 was essential for the interaction with LC3 and rescue of autophagy flux in shFAIM2 cells while LC3-binding property of FAIM2 was dispensable for the anti-apoptotic function in response to Fas receptor-mediated apoptosis. Suppression of autophagosome maturation was also observed in a null mutant of Caenorhabditis elegans lacking xbx-6, the ortholog of FAIM2. Our study suggests that FAIM2 is a novel regulator of autophagy mediating autophagosome maturation through the interaction with LC3. © 2019 Federation of American Societies for Experimental Biology.
URI
http://hdl.handle.net/20.500.11750/10988
DOI
10.1096/fj.201901626R
Publisher
Federation of American Societies for Experimental Biology
Related Researcher
  • Author Yu, Seong-Woon Laboratory of Neuronal Cell Death
  • Research Interests Molecular mechanisms of neuronal cell death and neurodegeneration
Files:
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Collection:
Department of Brain and Cognitive SciencesThe K. Kim Lab of Neurobehavior and Neural Circuits1. Journal Articles
Department of Brain and Cognitive SciencesLaboratory of Neuronal Cell Death1. Journal Articles


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