Abstract
During aerobic respiration, mitochondria generate superoxide anion (O2•−), hydrogen peroxide (H2O2), and hydroxyl radical (HO•), and these reactive oxygen species (ROS) are detrimental to mitochondria. Mitochondrial damage is linked to a broad spectrum of pathologies such as Alzheimer’s disease, hemochromatosis, and diabetes. Mitochondria contain several enzymes for rapidly removing superoxide anion and hydrogen peroxide, but how they antagonize HO• is elusive, representing a loophole in the anti-ROS system. Herein, we discovered that Rhodanese 2 (Rdl2) is critical for maintaining the functionality and integrity of mitochondria under sub-lethal ROS stress in Saccharomyces cerevisiae. Rdl2 converts stable sulfur species (thiosulfate and dialkyl polysulfide) to reactive sulfane sulfur including persulfide that protects mitochondrial DNA via scavenging HO•. Surprisingly, hydrogen sulfide (H2S) promotes HO• production through stimulating the Fenton reaction, leading to increased DNA damage. Our study may reveal an ex-ante mean for antagonizing HO•, patching the loophole of the anti-ROS system in mitochondria.
Competing Interest Statement
The authors have declared no competing interest.