Reduction in the levels of CoQ biosynthetic proteins is related to an increase in lifespan without evidence of hepatic mitohormesis

Mitohormesis is an adaptive response induced by a mild mitochondrial stress that promotes longevity and metabolic health in different organisms. This mechanism has been proposed as the cause of the increase in the survival in Coq7(+/−) (Mclk1(+/−)) mice, which show hepatic reduction of COQ7, early mitochondrial dysfunction and increased oxidative stress. Our study shows that the lack of COQ9 in Coq9(Q95X) mice triggers the reduction of COQ7, COQ6 and COQ5, which results in an increase in life expectancy. However, our results reveal that the hepatic CoQ levels are not decreased and, therefore, neither mitochondrial dysfunction or increased oxidative stress are observed in liver of Coq9(Q95X) mice. These data point out the tissue specific differences in CoQ biosynthesis. Moreover, our results suggest that the effect of reduced levels of COQ7 on the increased survival in Coq9(Q95X) mice may be due to mitochondrial mechanisms in non-liver tissues or to other unknown mechanisms.