Urinary Multi-Omics Profiling Reveals Systemic Molecular Alterations in Progressive External Ophthalmoplegia

Area of Science:

• Neurogenetics
• Mitochondrial Biology
• Multi-omics

Background:

• Mitochondrial diseases (MDs) are heterogeneous neurogenetic disorders.
• Molecular diagnosis has advanced, but understanding pathogenic mechanisms and therapies lags.
• Identifying molecular drivers of phenotypic variability is crucial for therapeutic targets.

Purpose of the Study:

• Investigate molecular alterations in Progressive External Ophthalmoplegia (PEO), a rare mitochondrial disorder.
• Utilize a multi-omics approach to uncover disease mechanisms.
• Identify potential diagnostic and therapeutic targets for MDs.

Main Methods:

• Studied eight adult PEO patients and eight healthy controls.
• Employed a comprehensive multi-omics strategy: LC-MS/MS proteomics, UPLC-MS/MS metabolomics, ATR-FTIR spectroscopy.
• Applied chemometric multivariate analysis to identify molecular signatures.

Main Results:

• Observed distinct proteomic and metabolic patterns related to energy metabolism in PEO patients.
• Metabolomics revealed altered amino acid levels and disruptions in cysteine, methionine, and glutathione metabolism.
• Proteomics identified 154 differentially expressed proteins, implicating extracellular matrix organization and immune response pathways.

Conclusions:

• This integrative multi-omics approach provides novel insights into PEO molecular complexity.
• Identified disease-associated molecular signatures can advance understanding of pathogenic mechanisms.
• Findings may support the development of improved diagnostic and therapeutic strategies for MDs.