Abstract
Cysteine persulfide and polysulfide produced in cells exist in abundance in both low-molecular -weight and protein fractions. They can act as an antioxidant and thus protect cells from harmful free radicals and oxidative stress that may cause various diseases. However, how these reactive sulfur molecules are formed, or what role they play exactly within the cells and tissues, has not been well understood. We recently demonstrated that cysteinyl-tRNA synthetase (CARS) is novel cysteine persulfide synthase. CARS is involved in protein polysulfidation that is coupled with translation. The mitochondria biogenesis and bioenergetics are also supported and up-regulated by cysteine persulfide derived from mitochondrial CARS (also known as CARS2). Targeted and functional disruption of a gene encoding mitochondrial CARS (CARS2) and sulfide-quinone reductase (SQR) in mice revealed that persulfides derived from CARS2 are critically involved in the mitochondrial energy metabolism in cooperation with SQR, which is known for a long time as sulfur respiration in anaerobic microorganisms. CARS2- and SQR-dependent sulfur respiration could prolong life and increase the quality of life and may open up a new venue for diagnosis, prevention and treatment for various diseases.
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