Assembly of mitochondrial complexes in the brain of a rat model of Alzheimer

NOVACK, GISELA VANINA; GALEANO, PABLO; CASTAÑO, EDUARDO MIGUEL; CUELLO, AUGUSTO CLAUDIO; MORELLI, LAURA

Mendoza

Congreso; LVIII Reunión Anual de la Sociedad Argentina de Investigaciónes en Bioquímica y Biología Molecular; 2022

Sociedad Argentina de Investigaciónes en Bioquímica y Biología Molecular

Mitochondrial respiratory complexes (CI, CII, CIII and CIV) are associated in supercomplexes (SCx) (SCx1: I+III2+IIn; SCx2: I+III2+IV1, SCx3: I+III2+IV2, SCx4: I+III2+IV3 y SCx5: I2+III2). Although its role in mitochondrial respiration is still controversial, the study of SCx (dis)assembly is relevant to understand the causes of brain bioenergetic dysfunction reported in Alzheimer´s disease (AD). In this work we evaluated the organization of SCx in an animal model of AD-like brain amyloidosis, the McGill-R-Thy1-APP transgenic (Tg) and controls (CNT) rats. Mitochondria from the hippocampus of 9-12-month-old animals (n = 3-6/group) were isolated and the organization and abundance of SCx were analyzed by electrophoretic runs in native gels (BN-PAGE) stained with Coomassie Brilliant Blue G-250. The functionality of CI was assessed by in-gel activity. Densitometric analysis of the bands showed that Tg and CNT rats do not assemble SCx2 and SCx3, unlike that was reported in mice. By contrast, both genotypes (in cortex and hippocampus) assemble SC1; SC4 (respirosome) and SC5; show the same amount of SC1 and the same respirosome (SC4) and SC5 activities. CNT and Tg show a significant decrease in the abundance of SC4 and SC5 in cortex and there is a significant decrease in the activity of SC1 in the cortex and hippocampus of Tg vs. CNT. Our results support the plastic model of organization of mitochondrial complexes in rat brain. We discard the hypothesis that the assembly of SCx is interrupted by the accumulation of amyloid at the early stages of the AD pathology and suggest that the decrease in SC1 activity (I+III2+IIn) could be the cause of the brain bioenergetic failure reported in this model.