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
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
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