Decrease in cytochrome c oxidase reserve capacity diminishes robustness of Drosophila melanogaster and shortens life span

The phenotypic effects of under- and over-expression of cytochrome c oxidase (CcO) regulatory subunits IV and Vb were examined in Drosophila melanogaster in order to further test the hypothesis that suppression of the activities of mitochondrial electron transport chain (ETC) oxidoreductases retards the aging process and extends life span. Under-expression of both CcO subunits, induced by RNAi, resulted in decreases in the respective mRNA and protein levels, CcO holoenzyme activity, rate of mitochondrial respiration, walking speed and the life span of flies. Over-expression of CcO IV or CcO Vb in young flies increased the amount of mRNA, but had no effect on the protein level or CcO catalytic activity. On the other hand, in older flies over-expression of CcO Vb, but not CcO IV, elevated the mRNA and protein amounts as well as the CcO holoenzyme activity, thereby, preventing the typical age-related decline in CcO activity. Nevertheless, life spans of the flies over-expressing CcO IV or Vb were neither extended nor shortened. Results demonstrate that: (i) the suppression of CcO function exerts deleterious rather than benign effects on fitness and survival, and (ii) the structure/function of CcO, an ETC oxidoredutase, can be “re-engineered” in vivo.

Source: BJ Energy - January 21, 2014 Category: Biochemistry Authors: V Klichko, B H. Sohal, S N. Radyuk, W C. Orr, R S. Sohal Tags: BJ Energy Source Type: research