PXD063066-1

PXD063066 is an original dataset announced via ProteomeXchange.

Title	CLUH inhibition by Lipocalin-2 orchestrates mitochondrial disruption and contributes to kidney disease
Description	Lipocalin-2 (LCN2) is a secreted protein involved in transporting hydrophobic molecules, regulating antibacterial responses and iron homeostasis. LCN2 expression is induced in response to kidney damage, and participates to chronic kidney disease (CKD) onset. We previously identified LCN2 as a key regulator of mitochondrial dysfunction in renal tubular cells contributing to kidney injury. In this study, we characterized LCN2 interactome to better understand its role in mitochondrial dysfunction and kidney pathology. We identified Clustered Mitochondrial Homolog (CLUH) as protein partner of LCN2. CLUH regulates mitochondrial homeostasis by binding mRNAs of nuclear-encoded mitochondrial proteins and promoting their translation. We demonstrated that LCN2 interaction with CLUH inhibits its activity, leading to mitochondrial clustering around the nucleus. We showed that CLUH is expressed in nephron and that its expression and activity decrease while LCN2 expression increases following kidney injury leading to CKD. In human CKD patients, CLUH expression is inversely correlated with kidney lesions and loss of function. Genetic CLUH deletion in renal tubular cells induces mitochondrial dysfunction, metabolic shift, and oxidative stress ultimately contributing to renal pathology. Our results underscore the critical role of CLUH in maintaining mitochondrial integrity and its interplay with LCN2 in renal disease progression.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_16:19:50.626.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cerina Chhuon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	biotinylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-17 06:50:06	ID requested
⏵ 1	2026-09-06 16:19:51	announced

10.1681/asn.0000000961;

Marques E, Alves Teixeira M, Ramauge Parra C, Isnard P, Kelly-Aubert M, Nguyen C, Lake J, Nemazanyy I, Rugarli EI, Terzi F, Gallazzini M, Clustered Mitochondrial Homolog Inhibition by Lipocalin-2 Orchestrates Mitochondrial Disruption and Contributes to Kidney Disease. J Am Soc Nephrol, 37(6):1174-1190(2026) [pubmed]

submitter keyword: BioID, Kidney, LCN2

Chiara Guerrera
contact affiliation	Proteomics Platform 3P5-Necker, - Structure Fédérative de Recherche Necker, Inserm US24/CNRS UAR 3633, Université Paris Cité, 75015, Paris, France.
contact email	chiara.guerrera@inserm.fr
lab head
Cerina Chhuon
contact affiliation	Proteomics Platform Necker, PPN-3P5, Structure Fédérative de Recherche SFR Necker, Université Paris Descartes, Paris, France
contact email	cerina.chhuon@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063066
     1. Label: PRIDE project
     2. Name: CLUH inhibition by Lipocalin-2 orchestrates mitochondrial disruption and contributes to kidney disease