coq7/clk‐1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q

Abstract

Summary coq7/clk-1 was isolated from a long-lived mutant ofCaenorhabditis elegans , and shows sluggish behaviours and an extended lifespan. In C. elegans and Saccharomyces cerevisiae , coq7/clk-1 is required for the biosynthesis of coenzyme Q (CoQ), an essential co-factor in mitochondrial respiration. The clk-1 mutant contains dietary CoQ 8 from Escherichia coli and demethoxyubiquinone 9 (DMQ9) instead of CoQ 9 . In a previous study, we generated COQ7-deficient mice by targeted disruption of the coq7 gene and reported that mouse coq7/clk-1 is also essential for CoQ synthesis, maintenance of mitochondrial integrity and neurogenesis. In the present study, we rescued COQ7-deficient mice from embryonic lethality and established a mouse model with decreased CoQ level by transgene expression of COQ7/CLK-1. A biochemical analysis showed a concomitant decrease in CoQ 9 , mitochondrial respiratory enzyme activity and the generation of reactive oxygen species (ROS) in the mitochondria of CoQ-insufficient mice. This implied that the depressed activity of respiratory enzymes and the depressed production of ROS may play a physiological role in the control of lifespan in mammalian species and of C. elegans .

Glyoxalase‐1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans

“…Studies of mutations affecting the lifespan in C. elegans as well as systematic screens of C. elegans genes using dsRNA (feeding RNAi) suggest that mitochondria and mitochondrial generation of reactive oxygen species (ROS) have a major causative role in the aging process (Shinohara et al ., 1998;Lee et al ., 2003;Turrens, 2003;Hartman et al ., 2004;Nakai et al ., 2004). There is strong evidence that caloric flux results in increased ROS formation, and that caloric restriction prolongs lifespan by decreasing ROS production via increased expression of PHA-4/Foxa, a dietary restrictionspecific activator of sod-1 , -2 , -4 , and -5 expression (Panowski et al ., 2007).…”

The biochemistry and cell biology of aging: metabolic regulation through mitochondrial signaling

“…clk-1 mutants are defective in mitochondrial respiration due to impaired electron transfer between complex I and complex III. This defect elevated the generation of ROS (127). The ROS thus generated apparently also did not shorten lifespan, but instead extended it.…”

Phenelzine Mitochondrial Functional Preservation and Neuroprotection after Traumatic Brain Injury Related to Scavenging of the Lipid Peroxidation-Derived Aldehyde 4-Hydroxy-2-Nonenal

“…[1][2][3][4] Brain mitochondrial dysfunction has been firmly associated with excitotoxicity, oxidative damage and metabolic perturbations. [5][6][7] Changes in mitochondrial function, such as suppression of mitochondrial oxidative phosphorylation, accumulation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and impaired calcium buffering have been shown to play a key role in induction of posttraumatic brain cell death. 8 Recent studies have demonstrated that much of the mitochondrial failure is mediated by ROS-induced lipid peroxidation (LP).…”