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Microbes & Immunity

ORIGINAL RESEARCH ARTICLE
Investigation of hydrogenase enzymes and the

presence of orthologs in the human proteome

Grace Russell *
1,2
1 Department of Research and Development, Water Fuel Engineering, Wakefield, Yorkshire,
United Kingdom
2 School of Applied Science, College of Health and Social Sciences, University of the West of
England (UWE), Bristol, United Kingdom
(This article belongs to the Special Issue: Hydrogen and the Human Microbiome)

Abstract

Hydrogenase enzymes catalyze the reversible oxidation/reduction of hydrogen (H )
2
and play a crucial role in microbial energy metabolism, with significant implications
for human immunity. H , produced by gut microbes during fermentation or
2
administered exogenously, is vital in modulating oxidative stress and inflammation.
In the gastrointestinal tract, microbial H production can reach up to 13 L/day,
2
with approximately 71% of commensal bacteria capable of metabolizing H .
2
By interacting with complex I, particularly the NDUFS7 subunit, H₂ may reduce
mitochondrial electron leakage and limit the generation of reactive oxygen species
(ROS). Excessive ROS can trigger pro-inflammatory signaling and impair immune
responses. This study investigated the presence of hydrogenase orthologs in the
human proteome, particularly within mitochondrial complex I, and their potential
role in immune function. This novel research highlights a possible evolutionary link
*Corresponding author:
Grace Russell between microbial hydrogenases and human immunity, suggesting that microbial-
(grace.russell@uwe.ac.uk) derived H may support immune homeostasis by mitigating oxidative stress and
2
inflammation. Although human homologs of nickel/iron hydrogenases, such as
Citation: Russell G. Investigation
of hydrogenase enzymes and the NDUFS2 and NDUFS7, likely lack classical hydrogenase activity, sequence similarities
presence of orthologs in the human between NDUFS7 and hydrogenase subunits in Asgard archaea and δ-proteobacteria
proteome. Microbes & Immunity. indicate the conservation of potential redox-active sites. Redox activity, occurring at
2024;1(2):81-93.
doi: 10.36922/mi.4544 the N2 iron-sulfur cluster in NDUFS7, may influence mitochondrial oxidative stress
responses, which are integral to immune regulation. These findings open new
Received: August 15, 2024
avenues for exploring the therapeutic potential of H₂ in immune regulation.
Accepted: October 10, 2024
Published Online: November 18, Keywords: Complex I; Evolution; Hydrogen; Hydrogenases; Redox activity; NDUFS7;
2024
Oxidative stress
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, 1. Introduction
and reproduction in any medium,
provided the original work is The intestinal microbiome plays a fundamental role in regulating immune function and
properly cited. mitigating oxidative stress, serving as a critical interface between host systems and the
Publisher’s Note: AccScience external environment. Comprising a vast array of microorganisms, the gut microbiome
Publishing remains neutral with not only modulates innate and adaptive immune responses but also defends against
regard to jurisdictional claims in 1
published maps and institutional pathogens while maintaining immune homeostasis. A key mechanism through which
affiliations. the microbiome influences immune health is the production of short-chain fatty acids

Volume 1 Issue 2 (2024) 81 doi: 10.36922/mi.4544