Dataset Information

An updated inventory of genes essential for oxidative phosphorylation identifies a mitochondrial origin in familial Ménière’s disease - Quantitative K562 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): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Meniere's Disease

SUBMITTER: Alexis Jourdain

LAB HEAD: Alexis Jourdain

PROVIDER: PXD060163 | Pride | 2025-07-30

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20231012_160604_Harhai_16654-TIMS.kit	Other
	5802_Harhai_DIA_16626_140min_4ul.d.zip	Other
	5803_Harhai_DIA_16625_140min_4ul.d.zip	Other
	5804_Harhai_DIA_16624_140min_4ul.d.zip	Other
	5805_Harhai_DIA_16623_140min_4ul.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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