PXD069152-1

PXD069152 is an original dataset announced via ProteomeXchange.

Title	EFHD1 promotes hepatocyte injury in metabolic liver disease by triggering Ca2+-dependent mitochondrial fission
Description	Human genome-wide association studies (GWAS) of metabolic-associated steatohepatitis (MASH), the most common liver disease worldwide, have examined either liver injury biomarkers or liver fat content, with lipid metabolism enzymes ranked highly in both analyses. Here, to define pathophysiological pathways independent of lipid metabolism, we focused on a gene of unknown function found in liver biomarker but not liver fat GWAS, EF-Hand Domain Family Member D1 (EFHD1). We now identify EFHD1 as the factor transducing endoplasmic reticulum calcium (Ca2+) release into a mitochondrial fission signal. Mechanistically, EFHD1 ablation prevented Ca2+-dependent actin rearrangements that support fission. Moreover, EFHD1 was critical for increased hepatocyte mitochondrial fission noted during MASH, and promoted cytoplasmic release of mitochondrial double-stranded RNA, a damage-associated molecular pattern driving an integrated stress response and injury via the protein kinase PKR. Finally, acutely inhibiting EFHD1 in mice developing MASH did not substantially alter steatosis but blunted hepatocyte injury, inflammation, and fibrosis.
HostingRepository	PRIDE
AnnounceDate	2026-07-31
AnnouncementXML	Submission_2026-07-30_21:24:52.804.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ryan Bia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-06 03:30:18	ID requested
⏵ 1	2026-07-30 21:24:53	announced

Dataset with its publication pending

submitter keyword: Mouse, EFHD1, Liver, MASH

Sarah Franklin
contact affiliation	CVRTI, University of Utah
contact email	sarah.franklin@utah.edu
lab head
Ryan Bia
contact affiliation	University of Utah
contact email	ryan.bia@utah.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069152
     1. Label: PRIDE project
     2. Name: EFHD1 promotes hepatocyte injury in metabolic liver disease by triggering Ca2+-dependent mitochondrial fission