PXD076314-1

PXD076314 is an original dataset announced via ProteomeXchange.

Title	Nitrate-Sialin2 Axis Couples ER-Mitochondrial Calcium Signaling with Fatty Acid Metabolism to Drive White Adipose Browning
Description	Nutrient cues shape adipose homeostasis; however, the mechanism by which inorganic signals engage organelle networks to drive white fat browning remains unclear. Here, we identify a nitrate-Sialin2 pathway that converts dietary nitrate into a spatially confined thermogenic program. Sialin2 localizes to mitochondria and endoplasmic reticulum (ER) to strengthen ER-mitochondria contacts and engage the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial calcium uniporter 1 (MCU1) conduit, boosting inducible mitochondrial Ca2+ uptake. In parallel, Sialin2 associates with lysosomal acid lipase (LIPA), Acyl-CoA Synthetase Long Chain Family Member 3 (ACSL3), and carnitine palmitoyltransferase 1A (CPT1A) to direct lipid-droplet-derived fatty acids into β-oxidation, thereby fueling the tricarboxylic acid (TCA) cycle and uncoupling protein 1 (UCP1)-dependent respiration. Loss of Slc17a5 abolishes nitrate-evoked browning and metabolic benefits, whereas nitrate supplementation improves adipose thermogenesis and systemic indices in diet-induced obesity without adrenergic stimulation. These findings reveal an organelle-specific nitrate-sensing mechanism that couples ionic signaling with substrate routing to reprogram adipocytes, providing a non-hormonal strategy for restoring metabolic homeostasis.
HostingRepository	PRIDE
AnnounceDate	2026-05-20
AnnouncementXML	Submission_2026-05-19_20:59:53.808.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ou Jiang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-30 05:02:29	ID requested
⏵ 1	2026-05-19 20:59:54	announced

Dataset with its publication pending

submitter keyword: Nitrate

Sialin2

ER-mitochondria contacts

calcium signaling

Lipid mobilization

Adipose browning

Jiang Ou
contact affiliation	Beijing, You An Men Wai Xi Tou Tiao No.10 Capital Medical University, Beijing Laboratory of Oral Health
contact email	010744@ccmu.edu.cn
lab head
Ou Jiang
contact affiliation	Capital Medical University
contact email	010744@ccmu.edu.cn
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/2026/05/PXD076314

PRIDE project URI

• PRIDE
  1. PXD076314
     1. Label: PRIDE project
     2. Name: Nitrate-Sialin2 Axis Couples ER-Mitochondrial Calcium Signaling with Fatty Acid Metabolism to Drive White Adipose Browning