PMID- 26253785
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20211203
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 43
IP  - 2
DP  - 2015 Aug 18
TI  - BNIP3- and BNIP3L-Mediated Mitophagy Promotes the Generation of Natural Killer 
      Cell Memory.
PG  - 331-42
LID - S1074-7613(15)00279-4 [pii]
LID - 10.1016/j.immuni.2015.07.012 [doi]
AB  - Natural killer (NK) cells are innate lymphocytes that possess traits of adaptive 
      immunity, such as clonal expansion, contraction, and generation of long-lived 
      "memory" cells, processes poorly understood at the molecular level. Here, we 
      found that as proliferating NK cells accumulated dysfunctional mitochondria 
      during viral infection, a protective mitophagy pathway was induced during the 
      contraction phase to promote their survival in a reactive oxygen species 
      (ROS)-dependent manner. Inhibition of mechanistic target of rapamycin (mTOR) or 
      activation of AMP-activated protein kinase (AMPK) during the 
      contraction-to-memory phase transition of the antiviral response increased 
      autophagic activity and enhanced memory NK cell numbers through an Atg3-dependent 
      mechanism. Furthermore, we demonstrated a temporally regulated role for 
      mitophagy-inducing proteins BCL2/adenovirus E1B 19-kDa interacting protein 3 
      (BNIP3) and BNIP3-like (BNIP3L) in the generation of robust NK cell memory. Thus, 
      our study reveals the functional importance of mitophagy during the dynamic 
      response of these cytolytic innate lymphocytes.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - O'Sullivan, Timothy E
AU  - O'Sullivan TE
AD  - Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, 
      USA.
FAU - Johnson, Lexus R
AU  - Johnson LR
AD  - Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, 
      USA.
FAU - Kang, Helen H
AU  - Kang HH
AD  - Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical 
      College, New York, NY 10065, USA.
FAU - Sun, Joseph C
AU  - Sun JC
AD  - Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, 
      USA; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical 
      College, New York, NY 10065, USA. Electronic address: sunj@mskcc.org.
LA  - eng
GR  - R01 AI100874/AI/NIAID NIH HHS/United States
GR  - AI085034/AI/NIAID NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R00 AI085034/AI/NIAID NIH HHS/United States
GR  - AI100874/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150804
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (BNip3 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Nix protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 6.3.2.- (Atg3 protein, mouse)
SB  - IM
CIN - Immunity. 2015 Aug 18;43(2):218-20. PMID: 26287678
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Autophagy-Related Proteins
MH  - Cells, Cultured
MH  - Herpesviridae Infections/*immunology
MH  - Immunologic Memory/genetics
MH  - Killer Cells, Natural/*immunology/virology
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria/*metabolism/virology
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Mitophagy/*genetics
MH  - Muromegalovirus/*immunology
MH  - Reactive Oxygen Species/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Ubiquitin-Conjugating Enzymes/metabolism
PMC - PMC5737626
MID - NIHMS925856
EDAT- 2015/08/09 06:00
MHDA- 2015/11/18 06:00
PMCR- 2017/12/20
CRDT- 2015/08/09 06:00
PHST- 2014/12/19 00:00 [received]
PHST- 2015/03/31 00:00 [revised]
PHST- 2015/05/29 00:00 [accepted]
PHST- 2015/08/09 06:00 [entrez]
PHST- 2015/08/09 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
PHST- 2017/12/20 00:00 [pmc-release]
AID - S1074-7613(15)00279-4 [pii]
AID - 10.1016/j.immuni.2015.07.012 [doi]
PST - ppublish
SO  - Immunity. 2015 Aug 18;43(2):331-42. doi: 10.1016/j.immuni.2015.07.012. Epub 2015 
      Aug 4.