{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:25:31Z","timestamp":1787163931712,"version":"build-2736575974"},"reference-count":81,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270744"],"award-info":[{"award-number":["32270744"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM140631"],"award-info":[{"award-number":["R35GM140631"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:p>\n                    Coordinated ciliary\/flagellar beating requires precise spatiotemporal regulation of molecular motors such as dyneins, yet the molecular mechanisms governing ciliary synchrony remain poorly understood. Here, we demonstrate that a heme-binding axonemal protein CYB5D1 functions as a redox-sensitive switch that controls flagellar beating coordination by regulating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics. Both the D58G point mutation, which abolishes heme-binding activity, and the complete loss of CYB5D1 lead to a reduction in the flagellar redox potential. More importantly, the hyperreductive intraflagellar redox shift in the\n                    <jats:italic toggle=\"yes\">cyb5d1<\/jats:italic>\n                    mutant increases\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    -flagellar Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spike frequency and amplitude, similar to reductive treatment of wild-type flagella, resulting in the loss of flagellar beating coordination. Interestingly, oxidative treatments induced synchronized Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spikes across both\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    - and\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -flagella of\n                    <jats:italic toggle=\"yes\">cyb5d1<\/jats:italic>\n                    and increased flagellar beating coordination. In addition, loss of CYB5D1 raised the intraflagellar Ca\n                    <jats:sup>2+<\/jats:sup>\n                    pool. These results indicate that CYB5D1 links redox sensing to Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling in ciliary coordination and reveal how the two flagella of the same cell achieve synchronized beating through redox-gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics. Furthermore, CYB5D1 loss impairs gliding motility by dysregulating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spiking specifically in the leading flagellum, extending the redox-Ca\n                    <jats:sup>2+<\/jats:sup>\n                    regulatory axis to surface-associated flagellar behaviors. Given the evolutionary conservation of both CYB5D1 and the redox-Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling axis, this mechanism likely regulates ciliary function across eukaryotes, with implications for understanding ciliopathies and respiratory diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2535939123","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:37:08Z","timestamp":1787161028000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Heme-binding protein CYB5D1 couples intraflagellar redox to calcium signaling for coordinated flagellar 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8303-194X","authenticated-orcid":false,"given":"Gai","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034t30j35","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-2763","authenticated-orcid":false,"given":"Xuan","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034t30j35","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5484-5530","authenticated-orcid":false,"given":"Stephen 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