PXD066527

PXD066527 is an original dataset announced via ProteomeXchange.

Title	TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence
Description	Entry and exit from cellular quiescence require dynamic adjustments in nutrient acquisition, yet the mechanisms by which quiescent cells downregulate amino acid (AA) transport remain poorly understood. Here we show that cells entering quiescence selectively target plasma membrane-resident AA transporters for endocytosis and lysosomal degradation. This process matches AA uptake with reduced translational demand and promotes survival during extended periods of quiescence. Mechanistically, we identify the α-arrestin TXNIP as a key regulator of this metabolic adaptation, since it mediates the endocytosis of the SLC7A5-SLC3A2 (LAT1-4F2hc) AA transporter complex in response to reduced AKT signaling. To promote transporter ubiquitination, TXNIP interacts with NEDD4L and other HECT-type ubiquitin ligases. Loss of TXNIP disrupts this regulation, resulting in dysregulated AA uptake, sustained mTORC1 signaling, and ultimately cell death under prolonged quiescence. The characterization of a novel TXNIP loss-of-function variant in a patient with a severe metabolic disease further supports its role in nutrient homeostasis and human health. Together, these findings highlight TXNIP's central role in controlling nutrient acquisition and metabolic plasticity with implications for quiescence biology and diseases.
HostingRepository	PRIDE
AnnounceDate	2025-12-08
AnnouncementXML	Submission_2025-12-07_16:19:55.532.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Leopold Kremser
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-24 04:24:19	ID requested
⏵ 1	2025-12-07 16:19:56	announced

10.1038/s44318-025-00608-9;

Kahlhofer J, Marchet N, Zubak K, Seifert B, Hotze M, Egger-H, ö, rschinger AS, Kucej L, Manzl C, Weyer Y, Weys S, Offterdinger M, Herzog S, Reiterer V, Volani C, Kwiatkowski M, Wortmann SB, Nemati S, Mayr JA, Zschocke J, Radlinger B, Thedieck K, Kremser L, Sarg B, Huber LA, Farhan H, de Araujo MEG, Kaser S, Scholl-B, ü, rgi S, Karall D, Teis D, TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence. EMBO J, 44(23):7119-7153(2025) [pubmed]

submitter keyword: nutrient transporter, HECT-type ubiquitin ligase, PPxY, quiescence ,arrestin, endocytosis

David Teis
contact affiliation	Institute of Molecular Biochemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria
contact email	david.teis@i-med.ac.at
lab head
Leopold Kremser
contact affiliation	Medical University Innsbruck
contact email	leopold.kremser@i-med.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066527
     1. Label: PRIDE project
     2. Name: TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence