Mitochondrial Proteomics

Mitochondria are important organelles of eukaryotic cells and play a key role in the regulation of cellular energy metabolism, biosynthesis and cell death (including apoptosis and programmed cell necrosis). In addition, mitochondria are involved in important physiological processes such as tricarboxylic acid cycle, fatty acid and amino acid oxidation, and regulation of calcium ion homeostasis. Since mitochondria play an important role in the maintenance of homeostasis, their abnormal function is associated with many human diseases, such as neurodegenerative diseases, cancer, heart disease and diabetes.

Mutations in more than 350 genes of mitochondrial and nuclear origin have been reported, resulting in mitochondrial diseases. Mutations result in OXPHOS dysfunction or other disturbances in mitochondrial structure and function, including disturbances in mitochondrial ultrastructure, abnormal cofactor and vitamin production, or impaired other metabolic processes within the mitochondria, including the tricarboxylic acid (TCA) cycle and pyruvate metabolism. Mitochondrial diseases exhibit heterogeneous phenotypic and biochemical manifestations. Variations coupled with incomplete understanding of mitochondrial pathophysiology make mitochondrial diseases diagnostically challenging and disease modifying therapies are lacking.

The rise of multi-omics technologies enables the detection of multiple molecular component differences in organisms, including genomics, transcriptomics, proteomics, and metabolomics. Sophisticated bioinformatics tools are able to reveal mitochondrial function and its contribution to cellular health and disease.

Abnormal expression of mitochondrial proteins is the main cause of their dysfunction. Mitochondrial proteomics analyzes the dynamic changes of protein composition, expression level and modification status of mitochondria from a holistic perspective, aiming to elucidate the expression and functional patterns of all proteins in mitochondria, including protein expression and presence mode (modification mode), structure and function, and protein interactions, so as to explore the connection between mitochondrial physiological functions and related diseases at the protein level.

Mitochondrial proteomics can be used to systematically study the differences in mitochondrial protein distribution and expression in normal and diseased tissues, thus laying the theoretical foundation for studying the molecular mechanisms of mitochondrial-related diseases and drug development using mitochondria as targets.

With the development of mitochondrial proteome extraction, isolation and identification technologies, it is now possible to analyze both the entire mitochondrial proteome and to target membrane gap or matrix subregion interproteome analysis. Proteomics provides a wealth of mitochondrial gene and protein information that, when combined with clinical features, facilitates the discovery of disease-related genes and proteins and provides a foundation for the systematic study of the relationship between mitochondria and human disease.

Creative Proteomics provides mitochondrial proteomics analysis services that enable detection of low abundance proteins, full mitochondrial protein profiling, and identification and characterization of specific proteins to assist in elucidating fundamental aspects of mitochondrial structure and function and provide new insights for improving the outcome of mitochondrial diseases.

Reference

Moro, L. (2020). The mitochondrial proteome of tumor cells: a SnapShot on methodological approaches and new biomarkers. Biology, 9(12), 479.