ABSTRACT
Coenzyme Q (CoQ) is an essential endogenously synthesized molecule that links different metabolic pathways to mitochondrial energy production thanks to its location in the mitochondrial inner membrane and its redox capacity, which also provide it with the capability to work as an antioxidant. Although defects in CoQ biosynthesis in human and mouse models cause CoQ deficiency syndrome, some animals models with particular defects in the CoQ biosynthetic pathway have shown an increase in life span, a fact that has been attributed to the concept of mitohormesis. Paradoxically, CoQ levels decline in some tissues in human and rodents during aging and coenzyme Q10 (CoQ10) supplementation has shown benefits as an anti-aging agent, especially under certain conditions associated with increased oxidative stress. Also, CoQ10 has shown therapeutic benefits in aging-related disorders, particularly in cardiovascular and metabolic diseases. Thus, we discuss the paradox of health benefits due to a defect in the CoQ biosynthetic pathway or exogenous supplementation of CoQ10.
Subject(s)
Aging , Ataxia , Mitochondrial Diseases , Muscle Weakness , Ubiquinone/analogs & derivatives , Ubiquinone/deficiency , Adult , Animals , Antioxidants , Caenorhabditis elegans , Diet , Female , Hormesis/physiology , Humans , Male , Mice , Middle Aged , Mitochondria/physiology , Rats , Young AdultABSTRACT
Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In the Coq9R239X mouse model with fatal mitochondrial encephalopathy due to CoQ deficiency, we have tested the therapeutic potential of ß-resorcylic acid (ß-RA), a structural analog of the CoQ precursor 4-hydroxybenzoic acid and the anti-inflammatory salicylic acid. ß-RA noticeably rescued the phenotypic, morphological, and histopathological signs of the encephalopathy, leading to a significant increase in the survival. Those effects were due to the decrease of the levels of demethoxyubiquinone-9 (DMQ9) and the increase of mitochondrial bioenergetics in peripheral tissues. However, neither CoQ biosynthesis nor mitochondrial function changed in the brain after the therapy, suggesting that some endocrine interactions may induce the reduction of the astrogliosis, spongiosis, and the secondary down-regulation of astrocytes-related neuroinflammatory genes. Because the therapeutic outcomes of ß-RA administration were superior to those after CoQ10 supplementation, its use in the clinic should be considered in CoQ deficiencies.
