Dataset Information

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

ABSTRACT: 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): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Meniere's Disease

SUBMITTER: Alexis Jourdain

LAB HEAD: Alexis Jourdain

PROVIDER: PXD060152 | Pride | 2025-07-30

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	7572_Harhai_DIA_18417_15SPD.d.zip	Other
	7573_Harhai_DIA_18418_15SPD.d.zip	Other
	7574_Harhai_DIA_18419_15SPD.d.zip	Other
	7575_Harhai_DIA_18420_15SPD.d.zip	Other
	7576_Harhai_DIA_18421_15SPD.d.zip	Other

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Publications

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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