Format

Send to

Choose Destination
Immunity. 2015 Aug 18;43(2):331-42. doi: 10.1016/j.immuni.2015.07.012. Epub 2015 Aug 4.

BNIP3- and BNIP3L-Mediated Mitophagy Promotes the Generation of Natural Killer Cell Memory.

Author information

1
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
2
Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065, USA.
3
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.

Abstract

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.

PMID:
26253785
PMCID:
PMC5737626
DOI:
10.1016/j.immuni.2015.07.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center