Stratification of mitochondrial disease patients in proteomics data. From Correia et al., 2024. “Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease“, JCI Insight. 2024;9(20):e178645. Licensed under an Attribution 4.0 international license.

Combining proteomics with genetic analysis, a recent study by Correia et al. has identified seven potential biomarkers for mitochondrial diseases. Researchers from the Wredenberg lab conducted mass spectrometry-based label-free proteomics analysis on primary fibroblasts from 67 patients with diagnosed or suspected mitochondrial disease and 17 control individuals.

The study successfully identified 5,888 unique proteins, with 674 localizing to mitochondria. Through differential expression analysis, they identified seven potential biomarkers that consistently distinguished between mitochondrial disease patients and controls. These included downregulated proteins MOXD1, MSRA, GPX4, and MORF4L1, associated with cellular stress responses, and upregulated proteins GABPA, CNBP, and TMED9.

The research revealed distinct proteomic signatures for different mitochondrial disease groups and demonstrated the potential of proteomics in supporting genetic diagnoses. Gene set enrichment analysis identified significant alterations in pathways related to mitochondrial function, inflammation, and cellular stress responses. The study validated the feasibility of integrating untargeted proteomics into routine diagnostic workflows for mitochondrial diseases.

This work was supported by high-quality chromatographic separations using an IonOpticks Aurora Ultimate 25×75 C18 UHPLC column for targeted proteomics validation, highlighting proteomics as a powerful tool to enhance diagnosis, identify biomarkers, and uncover disease mechanisms in mitochondrial disorders.

Publication
JCI Insight

Authors

Sandrina P. Correia, Marco F. Moedas, Lucie S. Taylor, Karin Naess, Albert Z. Lim, Robert McFarland, Zuzanna Kazior, Anastasia Rumyantseva, Rolf Wibom, Martin Engvall, Helene Bruhn, Nicole Lesko, Ákos Végvári, Lukas Käll, Matthias Trost, Charlotte L. Alston, Christoph Freyer, Robert W. Taylor, Anna Wedell, and Anna Wredenberg

Title

Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease