Regulatory circuits of mitophagy restrict distinct modes of cell death during memory CD8<sup>+</sup> T cell formation.

Details

Serval ID
serval:BIB_22AAC08FD04B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulatory circuits of mitophagy restrict distinct modes of cell death during memory CD8<sup>+</sup> T cell formation.
Journal
Science immunology
Author(s)
Franco F., Bevilacqua A., Wu R.M., Kao K.C., Lin C.P., Rousseau L., Peng F.T., Chuang Y.M., Peng J.J., Park J., Xu Y., Cassotta A., Yu Y.R., Speiser D.E., Sallusto F., Ho P.C.
ISSN
2470-9468 (Electronic)
ISSN-L
2470-9468
Publication state
Published
Issued date
29/09/2023
Peer-reviewed
Oui
Volume
8
Number
87
Pages
eadf7579
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Mitophagy, a central process guarding mitochondrial quality, is commonly impaired in human diseases such as Parkinson's disease, but its impact in adaptive immunity remains unclear. The differentiation and survival of memory CD8 <sup>+</sup> T cells rely on oxidative metabolism, a process that requires robust mitochondrial quality control. Here, we found that Parkinson's disease patients have a reduced frequency of CD8 <sup>+</sup> memory T cells compared with healthy donors and failed to form memory T cells upon vaccination against COVID-19, highlighting the importance of mitochondrial quality control for memory CD8 <sup>+</sup> T cell formation. We further uncovered that regulators of mitophagy, including Parkin and NIX, were up-regulated in response to interleukin-15 (IL-15) for supporting memory T cell formation. Mechanistically, Parkin suppressed VDAC1-dependent apoptosis in memory T cells. In contrast, NIX expression in T cells counteracted ferroptosis by preventing metabolic dysfunction resulting from impaired mitophagy. Together, our results indicate that the mitophagy machinery orchestrates survival and metabolic dynamics required for memory T cell formation, as well as highlight a deficit in T cell-mediated antiviral responses in Parkinson's disease patients.
Keywords
Humans, CD8-Positive T-Lymphocytes, Memory T Cells, Mitophagy, Parkinson Disease, COVID-19, Cell Death
Pubmed
Web of science
Create date
29/09/2023 14:40
Last modification date
25/11/2023 7:08
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