REVIEW: Reactive Halogen Species: Role in Living Systems and Current Research Approaches

---

Yuliya V. Khramova^1,2,a*, Veronika A. Katrukha^1,2, Victoria V. Chebanenko^1,2, Alexander I. Kostyuk^2,3, Nikolay P. Gorbunov⁴, Oleg M. Panasenko⁵, Alexey V. Sokolov^4,5,b*, and Dmitry S. Bilan^2,3,c*

¹Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

²Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

³Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia

⁴Institute of Experimental Medicine, 197022 Saint-Petersburg, Russia

⁵Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, 119435 Moscow, Russia

Received August 31, 2023; Revised September 21, 2023; Accepted October 4, 2023

---

Reactive halogen species (RHS) are highly reactive compounds that are normally required for regulation of immune response, inflammatory reactions, enzyme function, etc. At the same time, hyperproduction of highly reactive compounds leads to the development of various socially significant diseases – asthma, pulmonary hypertension, oncological and neurodegenerative diseases, retinopathy, and many others. The main sources of (pseudo)hypohalous acids are enzymes from the family of heme peroxidases – myeloperoxidase, lactoperoxidase, eosinophil peroxidase, and thyroid peroxidase. Main targets of these compounds are proteins and peptides, primarily methionine and cysteine residues. Due to the short lifetime, detection of RHS can be difficult. The most common approach is detection of myeloperoxidase, which is thought to reflect the amount of RHS produced, but these methods are indirect, and the results are often contradictory. The most promising approaches seem to be those that provide direct registration of highly reactive compounds themselves or products of their interaction with components of living cells, such as fluorescent dyes. However, even such methods have a number of limitations and can often be applied mainly for in vitro studies with cell culture. Detection of reactive halogen species in living organisms in real time is a particularly acute issue. The present review is devoted to RHS, their characteristics, chemical properties, peculiarities of interaction with components of living cells, and methods of their detection in living systems. Special attention is paid to the genetically encoded tools, which have been introduced recently and allow avoiding a number of difficulties when working with living systems.

---

KEY WORDS: reactive halogen species, myeloperoxidase, lactoperoxidase, eosinophil peroxidase, thyroid peroxidase, peroxidasin, genetically encoded probes

DOI: 10.1134/S0006297924140062

---