Dataset Information

An updated inventory of genes essential for oxidative phosphorylation identifies a mitochondrial origin in familial Ménière’s disease - Quantitative mouse tissue proteomics

ABSTRACT: Mitochondrial disorders (MDs) are among the most common inborn errors of metabolism and primarily arise from defects in oxidative phosphorylation (OXPHOS). Their complex mode of inheritance and diverse clinical presentations render the diagnosis of MDs challenging and, to date, most lack a cure. Here, we build on previous efforts to discover genes necessary for OXPHOS and report a highly complementary galactose-sensitized CRISPR-Cas9 “growth” screen, presenting an updated inventory now with 481 OXPHOS genes, including 157 linked to MDs. We further focus on FAM136A, a gene associated with Ménière’s disease and show that it supports inter-membrane space protein homeostasis and OXPHOS in cell lines, mice, and patients. Our study identifies a mitochondrial basis in a familial form of Ménière’s disease (fMD), provides a comprehensive resource of OXPHOS-related genes, and sheds light on the pathways involved in mitochondrial disorders, with the potential to guide future diagnostics and treatments for MDs.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Brain, Liver

SUBMITTER: Alexis Jourdain

LAB HEAD: Alexis Jourdain

PROVIDER: PXD060278 | Pride | 2025-07-30

REPOSITORIES: Pride

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			Action	DRS
	20240521_124222_Jourdain-17631-TIMS.kit	Other
	6665_Jourdain_DIA_17174_15SPD.d.zip	Other
	6666_Jourdain_DIA_17173_15SPD.d.zip	Other
	6667_Jourdain_DIA_17172_15SPD.d.zip	Other
	6668_Jourdain_DIA_17171_15SPD.d.zip	Other

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An updated inventory of genes essential for oxidative phosphorylation identifies a mitochondrial origin in familial Ménière's disease.

Harhai Marcell M Foged Mads M MM Zarges Christine C Landoni Juan C JC Chollet Sylvain S Simonelli Michele M Recazens Emeline E Lisci Miriam M Laban Nora N Manley Suliana S Riemer Jan J Lopez-Escamez Jose Antonio JA Lysakowski Anna A Jourdain Alexis A AA

Cell reports 20250725 8

Mitochondrial disorders (MDs) are among the most common inborn errors of metabolism, and dysfunction in oxidative phosphorylation (OXPHOS) is a hallmark. Their complex mode of inheritance and diverse clinical presentations render the diagnosis of MDs challenging, and, to date, most lack a cure. Here, we build on previous efforts to identify genes necessary for OXPHOS and report a highly complementary galactose-sensitized CRISPR-Cas9 "growth" screen, presenting an updated inventory of 481 OXPHOS ...[more]

PMID: 40714634

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