Sulfur respiration in mammals:

A simple question whether we can survive on the earth without oxygen?

This question still being difficult to answer, but sulfur is one of things that can answer this question.
Sulfur may exist everywhere, land, ocean, and atmospheric. It comes from many sources in our
environment. Sulfur has many diverse allotropes like powder, stone etc. traits of sulfur is more
reactive and more useful in our life.

Sulfur mediates a fundamental and primitive energy metabolism. Sulfur is serving as an electron
acceptor ,mediating sulfur respiration in bacteria and sulfur respiration operated by a polysulfide
reductase in Wolinelaa helicobacteria. Sulfur respiration for energy production taking place in
hyperthermophilic bacteria Aquifex aeolicus and archaea. A centimeter long bacterium with DNA
contained metabolically active, membrane bound organelles, bacteria name thiomargarita magnifica.

Researchers have learned new information on the synthesis of a class of substances that are virtually
ubiquitous in living things and have been shown to be potent antioxidants that shield cells from free
radical damage. They discovered that these substances were also crucial for maintaining sulfur
respiration, a form of mitochondrial energy metabolism, which was previously unknown in
mammals, including humans.

Cysteine hydropersulfide (CysSSH) and other persulfides, as well as other chemicals, are widely
found in the cells of the majority of species, ranging from single-celled organisms to humans, as well
as in the natural environment and food. They are thought to function as an antioxidant that shields
cells from dangerous free radicals, byproducts of regular cell function or contaminants, which can
cause a number of disorders, including cancer. However, it is still unclear how these reactive sulfur
compounds are created or precisely what function they serve within these cells.

Physiologically, prokaryotes, eukaryotic cells, and mammalian tissues contain cysteine

hydropersulfide (CysSSH). The presence of CysSSH, glutathione persulfide (GSSH), and longer
chain sulfur compounds in cultured cells and tissues in vivo in mice and humans has previously been
unambiguously proven. Reactive persulfides, which are substances with an SSH group, are thought
to play a crucial role in cell-regulatory processes, according to the chemical characteristics and
abundance of these species. CysSSH and similar substances have been hypothesized to act as
powerful antioxidants and cellular protectors as well as potential redox signaling intermediates.
Several proteins and enzymes also require persulfides as structural elements. For example, they act
as metal ligands in iron-sulfur clusters (also known as sulfide donors) and in iron-cysteine and zinc-
cysteine complexes respectively. In actuality, the presence of a cell reservoir for cysteine
polysulfides coupled to proteins and low-molecular-weight (LMW) sulfane sulfur (sulfur-bonded
sulfur atoms with six electrons) has long been known.

Tohoku University researchers narrowed down one method for the synthesis of CysSSH inside cells
while collaborating with peers in Japan, Hungary, the United Kingdom, and the United States. They
published their results in Nature Communications. They discovered that the enzyme family known
as cysteinyl-tRNA synthetases (CARSs), which is prevalent in the majority of mammalian cells,
functions as the initial building block for the synthesis of CysSSH.

CARS enzymes come in two main varieties, one of which is found in the cytoplasm of cells and the
other in mitochondria. The scientists turned off the genes in mice and people that make the various
enzymes. They discovered that the majority of CysSSH and other persulfides are produced by an
enzyme located in the mitochondria.

The researchers discovered that when the enzyme is created inside the mitochondria, it leaves the
cell and travels to the cytoplasm, where it catalyzes the reaction that results in CysSSH. The enzyme
found inside mitochondria, which is frequently referred to as the "powerhouse of the cell," is also in
charge of generating energy and sustaining mitochondria.

The researchers discovered the dual functions that CARSs perform, highlighting their significance in
antioxidant defense and energy production. They permit the cells to have a route that supports sulfur
respiration without oxygen. This would open the door to study on how the enzymes might help treat
conditions including diabetes, chronic obstructive pulmonary disease (COPD), atherosclerosis, and
cardiovascular disease that are brought on by an increase in oxidants or by mitochondrial
dysfunction. This might extend life, improve quality of life, and possibly open up new opportunities
for cancer detection, prevention, and therapy.

This study reveals that cysteinyl-tRNA synthetases (CARSs), in addition to their canonical role in
protein translation, act as the principal cysteine persulfide synthases (CPERSs) in vivo. CARSs play
a novel and prominent role in endogenous production of both LMW polysulfides and polysulfidated
proteins that are abundantly detected in cells and in mice. Notably, CARS2, a mitochondrial isoform
of CARS, is involved in mitochondrial biogenesis and bioenergetics via CysSSH production.