Supersulfide biology and translational medicine for disease control.

For decades, the major focus of redox biology has been oxygen, the most abundant element on Earth. Molecular oxygen functions as the final electron acceptor in the mitochondrial respiratory chain, thus contributing to energy production in aerobic organisms. In addition, oxygen-derived reactive oxygen species that include hydrogen peroxide, oxygen and nitrogen free radicals, such as superoxide, hydroxyl radical, and nitric oxide radical, undergo a complicated sequence of electron transfer reactions with other biomolecules, which lead to their modified physiological functions and diverse biological and pathophysiological consequences (e.g. oxidative stress). What is now evident is that oxygen accounts for only a small number of redox reactions in organisms, and knowledge of the general landscape of biological redox reactions is still quite limited. This article discusses a new revision of redox biology, which is governed by redox-active sulfur-containing molecules - supersulfides. We define the term "supersulfides" as sulfur species with catenated sulfur atoms. Supersulfides were determined to be abundant in all organisms, but their redox biological properties have remained largely unexplored. In fact, the unique chemical properties of supersulfides permit them to be readily ionized or radicalized, thereby allowing supersulfides to actively participate in redox reactions and antioxidant responses in cells. Accumulating evidence has demonstrated that supersulfides are indispensable for fundamental biological processes such as energy production, nucleic acid metabolism, protein translation, and others. Moreover, manipulation of supersulfide levels was beneficial for pathogenesis of various diseases. Thus, supersulfide biology has opened a new era of disease control that includes potential applications to clinical diagnosis, prevention, and therapeutics of diseases.