BNIP3- and BNIP3L-mediated mitophagy promotes the generation of natural killer cell memory Journal Article
| Authors: | O'sullivan, T. E.; Johnson, L. R.; Kang, H. H.; Sun, J. C. |
| Article Title: | BNIP3- and BNIP3L-mediated mitophagy promotes the generation of natural killer cell memory |
| 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. After viral infection, the majority of effector lymphocytes undergo rapid apoptosis. However, it is unclear how a subset of these cells persist to form immunological memory. Sun and colleagues demonstrate that mitophagy promotes the survival of virus-specific NK cells during the contraction phase to promote memory. © 2015 Elsevier Inc. |
| Keywords: | controlled study; carrier protein; unclassified drug; nonhuman; animal cell; cell survival; cell protein; enzyme activation; mammalian target of rapamycin; rat; reactive oxygen metabolite; natural killer cell; virus infection; mitochondrion; adenoviridae; phase transition; hydroxymethylglutaryl coenzyme a reductase kinase; protein bnip3; mitophagy; priority journal; article; autophagy protein 3; protein bnip3 like |
| Journal Title: | Immunity |
| Volume: | 43 |
| Issue: | 2 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2015-08-18 |
| Start Page: | 331 |
| End Page: | 342 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2015.07.012 |
| PROVIDER: | scopus |
| PUBMED: | 26253785 |
| PMCID: | PMC5737626 |
| DOI/URL: | |
| Notes: | Export Date: 2 October 2015 -- Source: Scopus |
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