Mammalian cells produce and store cyclo-octasulfur, an eight-atom ring structure of elemental sulfur previously known in microorganisms, plants, and fungi. Researchers from institutions including Tohoku University and the Max Planck Institute for Polymer Research identified $S_8$ inside cellular mitochondria and lipid droplets. Their findings were published in the journal Science on September 24, 2026.
Detecting Elusive Sulfur Rings in Mammalian Tissues
Finding an insoluble ring molecule inside living mammalian cells required two complementary analytical techniques. Researchers deployed mass spectrometry utilizing a specialized polyaromatic capsule designed to capture and stabilize $S_8$, paired with Raman microscopy for direct visualization inside cellular structures. These methods revealed that while mitochondria maintain baseline levels, lipid droplets accumulate significantly higher concentrations of the elemental sulfur.
The analysis extended to pathological human tissue samples, uncovering striking accumulations of $S_8$ within breast cancer tissues compared to non-cancerous samples from identical patients. In specific clinical specimens, these concentrations exceeded 100 mM. Further investigation of exhaled breath condensate from breast tumor patients demonstrated elevated supersulfide metabolites when contrasted against healthy control groups. Nitric oxide synthases, including endothelial variants, actively contribute to this production within lipid droplets, demonstrating a metabolic function for these enzymes beyond simple nitric oxide generation.
Suppressing Lipid Peroxidation and Ferroptosis
Endogenous $S_8$ functions as a cellular shield against lipid damage and regulated cell death. When researchers depleted cellular reserves of $S_8$, lipid peroxidation escalated alongside ferroptosis, a specialized form of cell death driven by oxidized lipids. Supplying exogenous $S_8$ reversed this vulnerability, protecting adipocytes and endothelial cells from ferroptotic damage.
Biochemically, cyclo-octasulfur reacts directly with glutathione, a common cellular antioxidant molecule, to generate antioxidant supersulfides. These downstream products actively suppress lipid peroxidation. Testing this protective mechanism in a mouse model of osteoarthritis, local intra-articular administration of solubilized $S_8$ reduced levels of 4-hydroxynonenal, a biomarker for lipid peroxidation, suggesting that $S_8$ may protect joint tissues from oxidative injury.
The study, published in Science on September 24, 2026, establishes a previously unknown mammalian elemental sulfur system. Unlocking how organisms produce and regulate cyclo-octasulfur opens clinical avenues for addressing inflammatory disorders, metabolic conditions, aging-related pathologies, and oncological microenvironments.
