> J Biol Chem. 2008 Jul 17. [Epub ahead of print] Links
> Early mitochondrial dysfunction in long-lived Mclk1 +/- mice.Lapointe
> J, Hekimi S.
> Biology, McGill University, Montreal, Quebec H3A 1B1.
>
> Reduced activity of CLK-1/MCLK1 (aka COQ7), a mitochondrial enzyme
> that is necessary for ubiquinone biosynthesis, prolongs the lifespan
> of nematodes and mice by a mechanism that is distinct from that of the
> insulin signaling pathway. Here we show that two-fold reduction of
> MCLK1 expression in mice reveals an additional function for the
> protein, as this level of reduction does not affect ubiquinone levels
> yet affects mitochondrial function substantially. Indeed, we observe
> that the phenotype of young Mclk1 +/- mutants includes a severe
> reduction of mitochondrial electron transport, ATP synthesis, total
> nicotinamide adenine dinucleotide (NADtot) pool size, as well as an
> alteration in the activity of key enzymes of the TCA cycle.
> Surprisingly, we also find that Mclk1 heterozygosity leads to a
> dramatic increase in mitochondrial oxidative stress, by a variety of
> measures. Furthermore, we find that the mitochondrial dysfunction is ...