Rhodanese Rdl2 produces reactive sulfur species to protect mitochondria from reactive oxygen species

Mitochondria damage is related to a broad spectrum of pathologies including Alzheimer's, Parkinson's disease, and carcinogenesis. Recently, it has been found that reactive sulfur species (RSS) has a close connection with mitochondrial health. However, the enzyme involving in mitochondrial RSS generation and the mechanism of how RSS affects mitochondrial health are not well understood. In this study, we discovered that rhodanese 2 (Rdl2) is the main enzyme responsible for RSS generation in S. cerevisiae mitochondria, in which no sulfide: quinone oxidoreductase (Sqr) is present. Rdl2 releases sulfane sulfur atoms (S-0) from stable S-0 carriers (thiosulfate and dialkyl polysulfide) to produce RSS. Rdl2 deletion leads to morphological change, dysfunction, and DNA degradation of mitochondria. Rdl2-generated RSS can protect DNA from HO center dot attack. The reaction rate between RSS and HO center dot is similar to 10(10) M-1 s(-1), two magnitudes higher than that of HO center dot reacting with DNA. Surprisingly, hydrogen sulfide (H2S) promotes HO center dot production through stimulating the Fenton reaction, leading to increased DNA damage. This study highlights the antioxidation function of RSS in vivo and sheds a light on the elusive connection between RSS biogenesis and mitochondrial health.

Automated summary

The study revealed that rhodanese 2 is the main enzyme responsible for generating reactive sulfur species in yeast mitochondria. Deletion of Rdl2 leads to morphological changes, dysfunction, and DNA degradation of mitochondria, while the generated reactive sulfur species can protect DNA from hydroxyl radical attack.