PXD021508 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteome of WT and Usp30KO cytotoxic T lymphocytes |
Description | Recent work in immunometabolism has emphasised the role of mitochondria in both the innate and adaptive immune system. Mitochondria are important in T cell development and differentiation, but less is known about their role in CD8+ effector T cells (CTLs). We found that CTLs that lack the mitochondrial deubiquitinase USP30 undergo promiscuous mitophagy, destroying most of the cellular mitochondria. Surprisingly, this results in a markedly diminished killing capacity, while motility, signalling and secretion remain intact. This study uses quantitative DIA proteomics to measure the impact of USP30 deficiency on the global proteome of IL-2 maintained, 4.5 h TCR retriggered and 4.5 h TCR retriggered + cycloheximide CTL. Unexpectedly, inhibition of mitochondrial translation, through genetic or pharmacologic methods, was the mechanism by which CTL killing was impaired. Reduced mitochondrial translation triggered attenuated cytosolic translation which precluded replenishment of secreted effector molecules thereby limiting the capacity of CTLs to serially kill multiple targets. Thus, mitochondria emerge as a previously unappreciated homeostatic regulator of protein translation required for serial CTL killing. |
HostingRepository | PRIDE |
AnnounceDate | 2022-06-09 |
AnnouncementXML | Submission_2022-06-08_23:38:32.981.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Julia Marchingo |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Q Exactive HF-X |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-09-16 01:22:50 | ID requested | |
⏵ 1 | 2022-06-08 23:38:33 | announced | |
Publication List
Lisci M, Barton PR, Randzavola LO, Ma CY, Marchingo JM, Cantrell DA, Paupe V, Prudent J, Stinchcombe JC, Griffiths GM, Mitochondrial translation is required for sustained killing by cytotoxic T cells. Science, 374(6565):eabe9977(2021) [pubmed] |
Keyword List
submitter keyword: Mouse, T lymphocyte, Usp30, LC-MSMS, DIA |
Contact List
Gillian M. Griffiths |
contact affiliation | Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY, UK |
contact email | gg305@cam.ac.uk |
lab head | |
Julia Marchingo |
contact affiliation | School of Life Sciences, University of Dundee |
contact email | j.m.marchingo@dundee.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021508
- Label: PRIDE project
- Name: Proteome of WT and Usp30KO cytotoxic T lymphocytes