Ossabaw minipigs differ from other (mini)pig strains by their genetic predisposition to develop full metabolic syndrome and their non-responsiveness to cardioprotective interventions, even before developing the diseased phenotype. Previous DNA sequencing data revealed differences in a cluster of mitochondrial protein-coding genes between Ossabaw and Göttingen minipigs – a large animal model without such a genetic predisposition and a responsiveness to cardioprotection. Alterations in mitochondrial protein composition affect mitochondrial function, and mitochondria play a crucial role in the development of metabolic syndrome, and for cardioprotection. Therefore, we aimed to compare the cardiac mitochondrial proteome between lean Ossabaw minipigs with a healthy phenotype and Göttingen minipigs to gain initial insights into potential differences in mitochondrial protein composition and function. Cardiac mitochondria (left ventricular tissue) of both minipig strains (male/female pigs) were isolated and the proteome was analyzed by liquid chromatography-tandem mass spectrometry. An unbiased, non-hypothesis-driven proteome analysis, identified 97% overlap in the proteome. Among the 3% of differentially expressed proteins, 19 were related to mitochondrial metabolism, eight to transcription and translation, three to small molecule transport, two to oxidative phosphorylation, and one to dynamics and surveillance. These small differences in protein composition, were associated with an altered mitochondrial energy turnover - ATP production was reduced by 49% in Ossabaw compared to Göttingen minipig mitochondria. This proteome analysis provides a broader basis to understand how genetic alterations result in changes of the mitochondrial proteome and function, which might be relevant for the development and progression of metabolic syndrome and/or the primordial non-responsiveness to cardioprotection in Ossabaw minipigs.
Eickelmann et al. (Wed,) studied this question.