mAbDx collaborated on and provided novel monoclonal antibodies used in an Imaging Mass Spectrometry study entitled " A stagewise response to mitochondrial dysfunction in mitochondrial DNA maintenance disorders" that has been published in BBA - Molecular Basis of Disease (BBA - Molecular Basis of Disease 1870 (2024) 167131).

Imaging Mass Cytometry (IMC) allows simultaneous analysis of large number of protein targets in a single tissue section, while maintaining sufficient spatial resolution for single and sub-cellular analysis. This study characterized inherited mitochondrial Oxidative Phosphorylation (OXPHOS) deficiencies across all five OXPHOS complexes to better understand the response of muscle fibers to OXPHOS deficiency in patients with mtDNA maintenance disorders.

The study harnessed the power of Imaging Mass Cytometry to simultaneously probe 19 signaling proteins, four mitochondrial markers, and a muscle fiber marker. This allowed the examination of single fiber and sub-cellular levels and distribution of a range of key metabolic and signaling proteins. Combined OXPHOS Complex I and IV deficiencies were found to be the most common deficits. Interestingly, in fibers deficient for one or more OXPHOS complexes, the remaining complexes were often upregulated beyond the increase of mitochondrial mass typically observed in ragged red fibers. Further, OXPHOS deficient fibers exhibited an increase in the abundance of proteins involved in proteostasis, e.g. HSP60 and LONP1, and regulation of mitochondrial metabolism (including oxidative phosphorylation and proteolysis, e.g. PHB1). The analysis suggests that the cellular response to mitochondrial dysfunction changes depending on the combination of deficient oxidative phosphorylation complexes in each fiber.