PXD060812

PXD060812 is an original dataset announced via ProteomeXchange.

Title	Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue
Description	The distinctive color of brown adipose tissue (BAT) is attributed to its high content of heme-rich mitochondria. Despite this, the mechanisms by which BAT regulates intracellular heme levels remain largely unexplored. Here, we demonstrate that heme biosynthesis is the primary source of heme in brown adipocytes. Inhibiting heme biosynthesis results in an accumulation of the branched-chain amino acids (BCAAs) valine and isoleucine, due to a heme-associated metabolon that channels BCAA-derived carbons into heme biosynthesis. Heme synthesis-deficient brown adipocytes display reduced mitochondrial respiration and lower UCP1 levels compared to wild-type cells. While exogenous heme supplementation can restore intracellular heme levels and mitochondrial function, downregulation persists. This sustained UCP1 suppression is linked to epigenetic regulation induced by the accumulation of propionyl-CoA, a byproduct of disrupted heme synthesis. Finally, disruption of heme biosynthesis in BAT impairs thermogenic response and, in female, but not male, mice, hinders the cold- induced clearance of circulating BCAAs in a sex-hormone-dependent manner. These findings establish adipose heme biosynthesis as a key regulator of thermogenesis and sex-dependent BCAA homeostasis.
HostingRepository	PRIDE
AnnounceDate	2025-02-17
AnnouncementXML	Submission_2025-02-17_09:06:50.863.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joshua Coon
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-14 03:56:21	ID requested
⏵ 1	2025-02-17 09:06:51	announced

Dataset with its publication pending

submitter keyword: Mouse, Brown adipose, LC-MS/MS

Joshua J. Coon
contact affiliation	1 Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA 2 Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, USA 3 Morgridge Institute for Research, Madison, WI, USA 4 National Center for Quantitative Biology of Complex Systems, Madison, WI, USA
contact email	jcoon@chem.wisc.edu
lab head
Joshua Coon
contact affiliation	University of Wisconsin - Madison, Morgridge Institute for Research
contact email	jcoon@chem.wisc.edu
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/2025/02/PXD060812

PRIDE project URI

• PRIDE
  1. PXD060812
     1. Label: PRIDE project
     2. Name: Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue