Biologists who focus on human cells can tend to think of bacterial metabolism as a bizarre riot, irrelevant to their own fields. But researchers led by Takaaki Akaike at Tohoku University report that an eight-membered sulfur ring, once thought to be a bacterial curiosity, is produced in mammalian cells too (Science 2026, DOI: 10.1126/science.aec5473).
Sulfur is less abundant in biology than elemental heavy hitters like carbon, nitrogen, and oxygen—but where it appears, like in the amino acid cysteine and the metabolite glutathione, it tends to have an outsized role in biochemistry because of its reactivity. The elemental sulfur allotrope, cyclo-octasulfur or S8, is rarer still but has been detected in bacteria and fungi.
S8 is a crown-shaped, redox-neutral ring of elemental sulfur, and Akaike’s team developed a reagent to study it in cells. The reactant is a polyaromatic capsule with a hydrophobic cavity that captures S8 and a charged outer shell that enables mass spectrometry.
With this tool, and later with Raman microscopy, they didn’t find S8 only in bacteria and yeast but also in mouse and human cells.
“I have to say, I would not have thought to look for these [molecules] at all,” Jon Long, whose lab at Stanford University works on identifying new small-molecule metabolites in human biology, writes in an email to C&EN, adding that the detection is convincing.
Based on biochemical experiments, the researchers think glutathione is key to making the S8 in cells. Glutathione dimerizes through a sulfur-sulfur bond, and the researchers think an enzyme better known for nitric oxide synthesis can add additional sulfurs into the linkage between the two glutathione moieties. Eventually, they say, the sulfur chain becomes long enough to form a ring.
Cyclo-octasulfur is hydrophobic and clusters in energy-producing mitochondria and in lipid droplets, organelles that cells use to store fat. The researchers showed some evidence that S8 could act as an antioxidant, helping to prevent lipid oxidation. Long says he’d like to see more data on how this works. He also says the work opens big questions about how the ring fits into sulfur biology. Researchers have become very interested in understanding how cysteine, glutathione, and other sulfur-carrying metabolites contribute to aging and metabolic disease, and this new metabolite may thicken the plot.
