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bioRxiv · 10.1101/2021.07.19.452856

Rhodanese Rdl2 produces reactive sulfur species to scavenge hydroxyl radical and protect mitochondria

Wang, Q.·Chen, Z.·Zhang, X.·Xin, Y.·Xia, Y.·Xun, L.·Liu, H.
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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 Alzheimers 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.

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Wang, Q., Chen, Z., Zhang, X., Xin, Y., Xia, Y., Xun, L., Liu, H.. 2021-07-19. Rhodanese Rdl2 produces reactive sulfur species to scavenge hydroxyl radical and protect mitochondria. https://doi.org/10.1101/2021.07.19.452856

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