PXD026948

PXD026948 is an original dataset announced via ProteomeXchange.

Title	Doxycycline treated 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. We also measured the impact of pharmacologically inhibiting mitochondrial translation by performing Quantitative DIA proteomics on IL2 maintained or TCR retriggered CTL treated with the mitochondrial translation inhibitor doxycycline for 4.5 hrs. 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_22:01:02.593.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	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-27 15:50:22	ID requested
⏵ 1	2022-06-08 22:01:03	announced

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]

submitter keyword: Mouse, T cell, CTL, doxycycline, protein translation, mitochondria, DIA

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

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PRIDE project URI

• PRIDE
  1. PXD026948
     1. Label: PRIDE project
     2. Name: Doxycycline treated cytotoxic T lymphocytes