The alternative oxidase, a tool for compensating cytochrome c oxidase deficiency in human cells (original) (raw)

In plants as well as in a number of micro‐organisms, and in several animal phyla, but not in mammals, the alternative oxidase (AOX) possibly by‐passes the cytochrome segment of the respiratory chain. The AOX is located at the inner surface of the inner mitochondrial membrane, being activated by over‐reduction of the quinone pool and accumulation of keto‐acids such as pyruvate. Since these conditions are frequently encountered in patients with mitochondrial diseases, we hypothesized that the expression of the ascidian Ciona intestinalis AOX might alleviate the consequences of a blockade of the cytochrome segment of the respiratory chain in human cells. We previously expressed the C. intestinalis AOX in human embryonic kidney (HEK 293‐T‐derived) cells conferring cyanide‐resistance to cell respiration without any detectable detrimental effect (Hakkaart et al. 2006). We have now expressed the AOX in human cultured fibroblasts either with a functional respiratory chain (foreskin immortal...