REVIEW article
Front. Physiol.
Sec. Redox Physiology
This article is part of the Research TopicExploring sulfur compounds' role in inflammation and therapeutic potentialView all 6 articles
Enzymes that generate and regulate intracellular persulfides and polysulfides: Mechanistic insights and inhibitors
Provisionally accepted
- Keio University, Minato, Japan
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Reactive sulfur species (RSS), which include various persulfides and polysulfides, are generated by multiple enzymes in vivo and play critical roles in mammalian physiological processes such as redox signaling, metabolic regulation, radical scavenging and anti-inflammatory responses. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) are well known to mediate endogenous production of hydrogen sulfide (H2S), and, together with the mitochondrial isoform of cysteinyl-tRNA synthetase (CARS2), are proposed to be major sources of intracellular persulfides and polysulfides. In mitochondria, enzymes involved in the sulfide oxidation pathway, including sulfide:quinone oxidoreductase (SQOR), persulfide dioxygenase (ETHE1) and thiosulfate sulfurtransferase (TST), also contribute to maintaining and regulating intracellular persulfide levels. Selective inhibitors targeting these enzymes are expected to be powerful tools for elucidating the functions of RSS, as well as having therapeutic potential. In this review, we present a comprehensive overview of these enzymes, focusing on their reaction mechanisms and inhibitors.
Keywords: mitochondrial respiration, Persulfide, polysulfide, Protein persulfide, Reactive sulfur species, Selective inhibitor, sulfide oxidation, Transsulfuration pathway
Received: 15 Jan 2026; Accepted: 19 Jan 2026.
Copyright: © 2026 Hirabayashi, Sasaki, Ohno, Takayama, Yamada and Hanaoka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kenjiro Hanaoka
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.