Inna N Shokolenko, Glenn L Wilson, and Mikhail F Alexeyev
This review discusses the recent criticisms of the mainstream view that a vicious cycle of ROS-induced mtDNA damage induces further ROS production and mtDNA damage. For instance, the authors cite evidence that chronic exposure of cells to rotenone (a complex I inhibitor and ROS generator) and hydrogen peroxide causes no significant increase in mtDNA mutation. Indeed, the superoxide radical inhibits the enzyme aconitase, suppressing the Krebs cycle and reducing the supply of NADH and FADH2, which reduces the electron flow through the ETC. Thus there may exist a negative feedback loop for ROS production in oxidative phosphorylation. The authors suggest that ROS may in fact contribute to adaptive signalling to mitigate the effects of ageing. For instance, naked mole-rats live almost 8 times longer than mice, and yet have a much higher oxidative burden, especially in their mtDNA.