PXD029637

PXD029637 is an original dataset announced via ProteomeXchange.

Title	Deficiency of the ER protein seipin results in generalised lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities in seipin deficient patient cells.Seipin localizes at endoplasmic reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes
Description	Deficiency of the ER protein seipin results in generalised lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities in seipin deficient patient cells. A subset of seipin is enriched at ER-mitochondria contact sites (MAMs) in human and mouse cells and localizes in the vicinity of calcium regulators SERCA2, IP3R and VDAC. Seipin association with MAM calcium regulators is stimulated by fasting-like stimuli, while seipin association with lipid droplets is promoted by lipid loading. Acute seipin removal does not alter ER calcium stores but leads to defective mitochondrial calcium import accompanied by a widespread reduction in Krebs cycle metabolites and ATP levels. In mice, inducible seipin deletion leads to mitochondrial dysfunctions preceding the development of metabolic complications. Together, these data suggest that seipin controls mitochondrial energy metabolism by regulating mitochondrial calcium influx at MAMs. In seipin deficient adipose tissue, reduced ATP production compromises adipocyte properties, contributing to lipodystrophy pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:54:48.097.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François GUILLONNEAU
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-09 06:08:12	ID requested
1	2022-01-18 03:29:22	announced
⏵ 2	2023-11-14 08:54:48	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: AP-MS, Mus musculus, Seipin, Calcium handling, Adipocyte,Orbitrap Fusion, bottom-up, MAMs, Mitochondria dysfunction

Xvier Prieur
contact affiliation	Université de Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, France.
contact email	xavier.prieur@univ-nantes.fr
lab head
François GUILLONNEAU
contact affiliation	ICO Angers
contact email	francois.guillonneau@parisdescartes.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029637
     1. Label: PRIDE project
     2. Name: Deficiency of the ER protein seipin results in generalised lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities in seipin deficient patient cells.Seipin localizes at endoplasmic reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes