Figure 1. Pioglitazone restores mitochondrial bioenergetics, dependent upon the presence of mitoNEET, following ex vivo calcium insult.

Naive cortical mitochondria were isolated from adult wild-type and mitoNEET null mice and challenged with calcium; dose response with Pioglitazone was conducted to examine bioenergetic rescue. (A) Pioglitazone (50 nM) is able to increase State V complex I-mediated maximal mitochondrial respiration in mitochondria isolated from wild-type C57BL/6 mice cortex exposed to a high calcium (Ca²⁺; 150nm/mg) environment. (B) However, in mitochondria isolated from the cortical tissue of mitoNEET null mice, the same calcium insult (150nm/mg protein) has no significant effect and ex vivo addition of Pioglitazone does not increase State V complex I-mediated maximal mitochondrial respiration. Line of 100% OCR corresponds to the normalized average respiration of isolated mitochondria isolated from both wild-type (A) and mitoNEET null (B) mice in the absence of Ca²⁺. Western blots insert shows presence of mitoNEET in wild-type C57BL/6 mice but not in mitoNEET null mice. One-way ANOVA, Compared Drug Treated to Ca²⁺ + Vehicle, Bonferroni Post-Hoc, N=3/group, mean ± SEM, F_5,17 = 15.77, **p=0.0015, *p=0.016 in wild-type mitochondria; F_5,17 = 0.10, mitoNEET null mitochondria.