PXD064511

PXD064511 is an original dataset announced via ProteomeXchange.

Title	Quantitative mass spectrometry of HAX1 WT and HAX1 KO promyelocytic cells reveal differences in amino acid synthesis and lipid metabolism
Description	part of a project: Granulocyte differentiation arrest in HAX1-deficient cells demonstrated in a new in vitro model of Kostmann disease, is caused by ineffective lipid droplet autophagy and fatty acids uptake. Molecular and metabolic mechanisms underlying congenital neutropenia in patients with HAX1 deficiency are not clear at the moment. It was demonstrated that HAX1 deficiency results in the arrest of neutrophil differentiation. Our studies of the effect of HAX1 deficiency on proteomic and metabolic profiles of promyelocytic cells have led to a conclusion that HAX1-deficient cells display differences in amino acid metabolism, specifically arginine, serine and aspartate. The analysis revealed significant upregulation of several proteins in HAX1-deficient cells, specifically argininosuccinate synthase (ASS1), an enzyme of arginine biosynthesis pathway, with the highest upregulation score, confirmed by Western blot. Moreover, Quantitative System Metabolism (QSM) analysis of the proteomic data has led to a conclusion, supported by specific tests, that fatty acid metabolism is affected in HAX1-deficient cells. This assumption was confirmed by experiments showing that the lipid droplet content is increased in HAX1-deficient cells, pointing to the accumulation of fatty acids that are not metabolized. Studies of autophagosome formation and function in HAX1 WT and knockout (KO) cells revealed that autophagy of lipid droplets is defective at the stage of the fusion with the lysosome. It is known that autophagy-dependent generation of free fatty acids is critical for neutrophil differentiation, therefore if HAX1 deficiency affects normal autophagy of lipids in promyeloblasts it should explain its effect on differentiation arrest.
HostingRepository	PRIDE
AnnounceDate	2026-04-22
AnnouncementXML	Submission_2026-04-22_02:25:13.611.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD064511
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ewa Sitkiewicz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-02 06:27:54	ID requested
⏵ 1	2026-04-22 02:25:14	announced

10.6019/PXD064511;

submitter keyword: HAX1, lipid metabolism, lipid droplet autophagy, Kostmann disease, neutrophil differentiation

Ewa A. Grzybowska
contact affiliation	Maria Sklodowska-Curie National Research Institute of Oncology Roentgena 5 street, 02-781 Warsaw, Poland
contact email	Ewa.Grzybowska@nio.gov.pl
lab head
Ewa Sitkiewicz
contact affiliation	Mass Spectrometry Laboratory Institute of Biochemistry and Biophysics Polish Academy of Sciences
contact email	ewa@ibb.waw.pl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064511
     1. Label: PRIDE project
     2. Name: Quantitative mass spectrometry of HAX1 WT and HAX1 KO promyelocytic cells reveal differences in amino acid synthesis and lipid metabolism