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Barayeu, U.* ; Ogata, S.* ; Takata, T.* ; Jung, M.* ; Matsunaga, T.* ; Morita, M.* ; Ida, T.* ; Lange, M.* ; Unno, Y.* ; Boushehri, S.* ; Greicius, P.* ; Nishimura, A.* ; Catti, L.* ; Pan, Y.* ; Zhang, T.* ; Shimizu, T.* ; Ushioda, R.* ; Nakabayashi, T.* ; Asamitsu, S.* ; Fusegawa, K.* ; Suzuki, T.* ; Ishida, T.* ; Tanda, N.* ; Watanabe, Y.* ; Tsuchiya, Y.* ; Yamaguchi, R.* ; Noguchi, S.* ; Mishima, E. ; Yano, F.* ; Arisawa, M.* ; Stuehr, D.J.* ; Xia, N.* ; Li, H.* ; Moosmann, B.* ; Gräter, F.* ; Aponte-Santamaría, C.* ; Olzmann, J.A.* ; Conrad, M. ; van der Vliet, A.* ; Dick, T.P.* ; Motohashi, H.* ; Yoshizawa, M.* ; Akaike, T.*

Mammals produce cyclo-octasulfur to suppress lipid peroxidation and ferroptosis.

Science 393:eaec5473 (2026)

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Open Access Green as soon as Postprint is submitted to ZB.

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Elemental sulfur is an evolutionarily ancient metabolite, yet its generation, storage, and function in animals have remained unclear. We show that mammals harbor elemental sulfur in the form of its most stable allotrope, cyclo-octasulfur (S₈). We found that S₈ accumulates to millimolar concentrations in mitochondrial membranes and in lipid droplets in both mouse and human cells. We further identified lipid droplet-associated nitric oxide synthase as a source of S₈ biosynthesis and found that S₈ accumulation in lipid droplets limits lipid peroxidation and suppresses ferroptosis. Accordingly, intra-articular injection of solubilized S₈ reduces lipid peroxidation in a mouse model of osteoarthritis. Together, these findings reveal an endogenous pool of S₈ in mammals that may protect cells from oxidative membrane damage by modulating cellular sensitivity to ferroptosis.

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Publication type Article: Journal article

Document type Scientific Article

Keywords Nitric-oxide Synthase; Particle Mesh Ewald; Elemental Sulfur; Molecular-dynamics; Force-field; Software News; Gui; Expression; Simulations; Algorithm

ISSN (print) / ISBN 0036-8075

e-ISSN 1095-9203

Journal Science

Quellenangaben Volume: 393, Issue: 6818, Article Number: eaec5473

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa

Reviewing status Peer reviewed

Institute(s) Institute of Metabolism and Cell Death (MCD)

Grants DFG
Bakar Spark award
NIH
Klaus Tschira Foundation
European Research Council (ERC)
German Research Council (DFG)
ERC
National Institutes of Health (NIH)
Japan Society for the Promotion of Science (JSPS)
JSPS KAKENHI
Japan Science and Technology Agency (JST), CREST, Japan
FOREST Program, Japan
Japan Agency for Medical Research and Development (AMED), Japan
Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan