Page 89 - MI-1-2

Microbes & Immunity Identifying hydrogenase orthologs in the human proteome

To understand the origins of these complex regulatory immune-related diseases. Within the context of innate
pathways, the ancient environmental conditions that may immunity, the evolution of complex I is central to
have contributed to the development of early biological immune regulation. It is conceivable that H influenced
2
membranes should be examined. Given the volatile the development of immune defense mechanisms by
chemistry of the Hadean Earth, circa 4 billion years ago, modulating the metabolic pathways responsible for ROS
it is plausible that the first membranes were formed generation.
not from organic materials but from minerals such The syntrophy theory of evolution 32,33 emphasizes H₂ as
as mackinawite. 22-27 These semi-permeable, inorganic a crucial intermediary in metabolic exchanges, particularly
protomembranes could form in the vicinity of submarine involving an H -consuming, sulfate-reducing δ-proteobacterial
2
alkaline hydrothermal vents, where reductive, electron- host, an H₂-releasing Asgard archaeon, and a sulfide-oxidizing
rich volcanic detritus is exposed to the acidic, proton- α-proteobacterium. Therefore, it is reasonable to propose that
rich oceanic waters, potentially providing the chemical H metabolism, facilitated by hydrogenase enzymes, played
2
disequilibrium and minerals necessary for organic life. 22,23 a key role in the early bioenergetic processes essential for the
As the Earth’s early atmosphere was likely composed evolution of complex life.
of reducing gases such as carbon monoxide, H and
2,
CH , it has been suggested that the ability to utilize iron The primary objective of this research was to
4
(Fe)- induced catalysis of H as a means of supplying investigate the potential evolutionary connection between
2
electrons and protons for energy production, evolved hydrogenases and the functional subunits of complex I
billions of years ago. Preiner et al. propose that minerals across various microorganisms that may have contributed
27
24
such as mackinawite and magnetite could serve as prebiotic to the evolution of eukaryotic cells. This study sought
hydrogenases, facilitating organic reactions. Therefore, to elucidate how hydrogenases might have influenced
from an evolutionary standpoint, it is possible that H was the development of bioenergetic systems critical to the
2
one of the first reducing agents exploited in early energy evolution of complex cellular and somatic functions,
metabolism, a phenomenon that now predominantly including the modulation of cellular redox potential and
occurs in the mitochondria of animals. immune responses.
Hydrogenase enzymes catalyze the reversible oxidation/ 2. Methods
-
+
reduction of H (H ↔ 2H + e ) and are found in all single- To explore the potential evolutionary link between
2
2
celled organisms and many multicellular organisms; 28-30 hydrogenases and the functional subunits of complex
however, they are not known to exist in animals and humans. I, this study examined three microorganisms
Recent research by Lu. indicates that complex I may have implicated in the syntrophic hypothesis of evolution:
31
retained hydrogenase-type activity. Hydrogenases can be a δ-proteobacterium (Desulfovibrio carbinolicus), an
categorized into specific phylogenic groups, namely (i) Asgard archaeon (Candidatus Heimdallarchaeota), and an
iron only, (ii) iron-iron, and (iii) nickel-iron ([Fe], [FeFe], α-proteobacterium (Rhodobacter sphaeroides).
and [NiFe], respectively). 28,29 Among these, the [NiFe]
hydrogenases are the most commonly occurring, present Mbh investigated in this study include: (i) Ca.
in a wide range of microbial species. Heimdallarchaeota MbhJ (Uniprot# A0A1Q9PFW3) and
MbhL (Uniprot# A0A1Q9PFM5), (ii) D. carbinolicus with
[NiFe] hydrogenases can be further divided into four subunits Hyd494 (Uniprot# A0A4P6HTH3) and Hyd258
classes: (i) membrane-bound hydrogenases (Mbh), (ii) (Uniprot# A0A4P61469), and (iii) R. sphaeroides HupL
nitrogen-fixing cytoplasmic hydrogenases, (iii) cytoplasmic (Uniprot# Q3J0L7), HupS (Uniprot# O86467), HupU
hydrogenases that utilize 8-hydroxy-5 deazaflavin (Uniprot# O86466), and HupV (Uniprot# Q3J0M0).
(coenzyme F420) as a low-potential redox co-factor,
and (iv) oxygen (O )-sensitive, membrane-bound, 2.1. Basic local alignment search tool (BLASTp)
2
energy-converting hydrogenases. 28,29 Of these subgroups, analysis
membrane-bound group iv hydrogenases exhibit activity To assess whether the hydrogenase proteins of interest
resembling that of mitochondrial complex I, 28,31 making retained homology within the human proteome, the
this group particularly relevant to the present discussion. BLASTp was employed to analyze the [NiFe] hydrogenase
The interaction between H , commensal microbes, enzyme sequences from all three species. 34
2
and the immune system forms a complex network with
significant implications for health and immune function. 2.2. Dot plot analysis
A deeper understanding of this relationship could lead Using the [NiFe] sequences, a bioinformatic matrix
to novel therapeutic strategies for gastrointestinal and analysis was conducted using the EMBOSS program to

Volume 1 Issue 2 (2024) 83 doi: 10.36922/mi.4544