McLaughlin 2020 Sci Rep
|McLaughlin KL, Kew KA, McClung JM, Fisher-Wellman KH (2020) Subcellular proteomics combined with bioenergetic phenotyping reveals protein biomarkers of respiratory insufficiency in the setting of proofreading-deficient mitochondrial polymerase. Sci Rep 10:3603.|
Abstract: The mitochondrial mutator mouse is a well-established model of premature aging. In addition to accelerated aging, these mice develop hypertrophic cardiomyopathy at ~13 months of age, presumably due to overt mitochondrial dysfunction. Despite evidence of bioenergetic disruption within heart mitochondria, there is little information about the underlying changes to the mitochondrial proteome that either directly underly or predict respiratory insufficiency in mutator mice. Herein, nLC-MS/MS was used to interrogate the mitochondria-enriched proteome of heart and skeletal muscle of aged mutator mice. The mitochondrial proteome from heart tissue was then correlated with respiratory conductance data to identify protein biomarkers of respiratory insufficiency. The majority of downregulated proteins in mutator mitochondria were subunits of respiratory complexes I and IV, including both nuclear and mitochondrial-encoded proteins. Interestingly, the mitochondrial-encoded complex V subunits, were unchanged or upregulated in mutator mitochondria, suggesting a robustness to mtDNA mutation. Finally, the proteins most strongly correlated with respiratory conductance were PPM1K, NDUFB11, and C15orf61. These results suggest that mitochondrial mutator mice undergo a specific loss of mitochondrial complexes I and IV that limit their respiratory function independent of an upregulation of complex V. Additionally, the role of PPM1K in responding to mitochondrial stress warrants further exploration.
• Bioblast editor: Plangger M
Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression
Organism: Mouse Tissue;cell: Heart, Skeletal muscle Preparation: Isolated mitochondria
Regulation: PCr;Cr Coupling state: LEAK Pathway: F, N, S HRR: Oxygraph-2k