Figure 4.

Mfn2 and Drp1 protein levels in cortical mitochondria. Representative WB for Mfn2 (A–C) and Drp1 (D–F) and their relative quantification normalized to porin protein levels in the cortex of 2-, 6- and 14-month-old 3xTg female and male mice and their respective controls. Data were analyzed by two-way ANOVA, and results are expressed as percent change from control mean of 100% ± SEM of n = 4–6 animals per group and Mfn2 protein levels were significantly different in cortical mitochondria as a function of sex (*** p < 0.001) in 2- and 6-month-old mice and genotype (*** p < 0.001) in 6- and 14-month-old mice, with a significant interaction effect between sex and genotype only in 2-month-old mice (** p < 0.01). Analysis of simple main effects showed significantly lower levels of Mfn2 in 3xTg males versus 3xTg females (*** p < 0.001) and downregulation in the 3xTg male mice compared to controls (p = 0.03). Drp1 protein levels were significantly different in cortical mitochondria as a function of sex in 2- and 6-month-old mice (*** p < 0.001 and ** p < 0.01 respectively), with a significant interaction effect between sex and genotype only in 6-month-old mice (*** p < 0.001). Here, levels of Drp1 were significantly higher in males than females in the C57BL/6 mouse (*** p < 0.001) and in the 3xTg female relative to their background control females (* p < 0.05). Drp1 was significantly reduced in 3xTg males relative to male control mice (* p < 0.05).