title: The viral restriction factor tetherin prevents leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) from association with beclin 1 and B-cell CLL/lymphoma 2 (Bcl-2) and enhances autophagy and mitophagy.
abstract: Tetherin has been characterized as a key factor that restricts viral particles such as HIV and hepatitis C virus on plasma membranes, acts as a ligand of the immunoglobulin-like transcript 7 (ILT7) receptor in tumor cells, and suppresses antiviral innate immune responses mediated by human plasmacytoid dendritic cells. However, the normal cellular function of Tetherin without viral infection is unknown. Here we show that Tetherin not only serves as a substrate of autophagy but itself regulates the initiation of autophagy. Tetherin interacts with the autophagy/mitophagy suppressor LRPPRC and prevents LRPPRC from forming a ternary complex with Beclin 1 and Bcl-2 so that Beclin 1 is released to bind with PI3KCIII (class III PI3K) to activate the initiation of autophagy. Suppression of Tetherin leads to impairment of autophagy, whereas overexpression of Tetherin causes activation of autophagy. Under mitophagic stress, Tetherin is concentrated on mitochondria engulfed in autophagosomes. Tetherin plays a general role in the degradation of autophagosomes containing not only the symbiotic mitochondria but also, possibly, the infected virus. Therefore, Tetherin may enhance autophagy and mitophagy to suppress tumorigenesis, enhance innate immune responses, or prevent T cell apoptosis or pyroptosis.
authors: From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030, the Jiangxi Research Institute of Ophthalmology and Visual Sciences, The Affiliated Eye Hospital of Nanchang University, Nanchang, 330006, China.
authors: Jing
authors: J
authors: Zou
authors: From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors: Wenjiao
authors: W
authors: Li
authors: the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, and.
authors: Anisha
authors: A
authors: Misra
authors: From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors: Fei
authors: F
authors: Yue
authors: From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors: Kun
authors: K
authors: Song
authors: From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors: Qi
authors: Q
authors: Chen
authors: the Jiangxi Research Institute of Ophthalmology and Visual Sciences, The Affiliated Eye Hospital of Nanchang University, Nanchang, 330006, China.
authors: Guanghua
authors: G
authors: Guo
authors: the Jiangxi Research Institute of Ophthalmology and Visual Sciences, The Affiliated Eye Hospital of Nanchang University, Nanchang, 330006, China.
authors: Jinglin
authors: J
authors: Yi
authors: the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, and.
authors: Jason T
authors: JT
authors: Kimata
authors: From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030, the Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas 77843 lliu@ibt.tamhsc.edu.
authors: Leyuan
authors: L
authors: Liu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D058851:GPI-Linked Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D063306:Mitophagy; D009363:Neoplasm Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D060066:Protein Interaction Maps; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; C491997:BECN1 protein, human; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C087940:LRPPRC protein, human
keywords: AIDS; Autophagy; B-cell Lymphoma 2 (Bcl-2); Beclin-1 (BECN1); Lysosome; Mitochondria; Mitophagy; PI3K
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