Differential expression of ascertained subunits of the electron transport chain. A quantitative mass-tag labelling proteomic technique, iTRAQ, and mass-spectrometric analysis of the brain proteins from single, double and triple transgenic mouse models revealed massive deregulation of 24 components mainly related to the mitochondrial respiratory chain complex (including complex V), antioxidant enzymes, and synaptic proteins. Functional analysis validated the proteomic approach by confirming the strongest defects of the respiratory capacity mainly at complexes I, IV and V in transgenic mice, at both the protein and activity level. Significantly changed expression of nuclear-encoded (Ndufs2, Ndufs8, Ndufb10, IV, Va, Vb, VIIa and D) and mitochondrial-encoded (COX II) complex subunits are highlighted in red. Complex I subunits: Ndufs2, NADH dehydrogenase (ubiquinone) Fe-S protein 2; Ndufs8, NADH dehydrogenase (ubiquinone) Fe-S protein 8; Ndufb10, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10. Complex IV subunits: II, Cytochrome c oxidase subunit 2; IV, Cytochorme c oxidase subunit IV isoform 1; Va, Cytochrome c oxidase polypeptide Va; Vb, Cytochrome c oxidase polypeptide Va; VIIa, Cytochrome c oxidase polypeptide VIIa-liver/heart. Complex V subunits: D, ATP synthase D chain. IMM, inner mitochondrial membrane; IMS, intermembrane space.