PXD023790

PXD023790 is an original dataset announced via ProteomeXchange.

Title	HAX1 controls mitochondrial proteostasis
Description	The relevance of mitochondrial proteostasis for the differentiation and function of hematopoietic and immune cells is unknown. Dissecting the HCLS1-associated protein X-1 (HAX1) –related protein network, we define a functional CLPB-HAX1-PRKD2-HSP27 axis with critical importance for the differentiation of neutrophil granulocytes and thus elucidate molecular mechanisms underlying congenital neutropenia in patients with mutations in HAX1 and CLPB. As shown by SILAC proteomics, CLPB and HAX1 control the balance of protein synthesis and persistence in mitochondria, leading to dysfunction of the respiratory complex 1. Impaired mitochondrial proteostasis is associated with decreased abundance of the serine-threonine kinase PRKD2 and Ser82-phosphorylated HSP27. Cellular defects in HAX1-/- cells can be functionally reconstituted by HSP27. Thus, mitochondrial proteostasis emerges as a critical mechanism governing the differentiation and function of neutrophil granulocytes.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-19_18:22:47.808.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marta Murgia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-25 02:36:38	ID requested
⏵ 1	2022-05-19 18:22:48	announced

Fan Y, Murgia M, Linder MI, Mizoguchi Y, Wang C, Ł, yszkiewicz M, Zi, ȩ, tara N, Liu Y, Frenz S, Sciuccati G, Partida-Gaytan A, Alizadeh Z, Rezaei N, Rehling P, Dennerlein S, Mann M, Klein C, HAX1-dependent control of mitochondrial proteostasis governs neutrophil granulocyte differentiation. J Clin Invest, 132(9):(2022) [pubmed]

submitter keyword: protein quality control, hematopoiesis, inborn errors of immunity, severe congenital neutropenia

Christoph Klein
contact affiliation	Department of Pediatrics, Dr. von Hauner Children’s Hospital and Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany
contact email	Christoph.Klein@med.uni-muenchen.de
lab head
Marta Murgia
contact affiliation	MPI Biochemistry
contact email	mmurgia@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/05/PXD023790

PRIDE project URI

• PRIDE
  1. PXD023790
     1. Label: PRIDE project
     2. Name: HAX1 controls mitochondrial proteostasis