{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T14:13:38Z","timestamp":1767017618590,"version":"3.48.0"},"posted":{"date-parts":[[2025,12,25]]},"group-title":"Biochemistry","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM133764"],"award-info":[{"award-number":["R35GM133764"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21AI185746"],"award-info":[{"award-number":["R21AI185746"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U54AI170856"],"award-info":[{"award-number":["U54AI170856"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Eukaryotic cytochrome (cyt)\n                  <jats:italic>c<\/jats:italic>\n                  is a highly conserved mitochondrial protein central to cellular respiration, featuring a covalently attached hexacoordinate heme whose redox potential is tuned by axial His\/Met ligands and surrounding residues to support electron transport chain (ETC) function. We have identified an unrecognized lineage of eukaryotic cyt\n                  <jats:italic>c<\/jats:italic>\n                  homologs in Apicomplexa, a phylum of intracellular pathogens that includes\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  malaria parasites.\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  cyt\n                  <jats:italic>c<\/jats:italic>\n                  -2 (Pfcyt\n                  <jats:italic>c<\/jats:italic>\n                  -2) exemplifies this divergent lineage and has an unusual pentacoordinate heme despite conservation of His\/Met ligands. We determined that Pfcyt\n                  <jats:italic>c<\/jats:italic>\n                  -2 has a redox potential of \u2013278 mV that is over 500 mV lower than canonical cyt\n                  <jats:italic>c<\/jats:italic>\n                  homologs (+250 mV) and contradicts a conserved ETC role. This anomalous redox potential is lower than any natural monoheme\n                  <jats:italic>c<\/jats:italic>\n                  -type cyt. Nevertheless, Pfcyt\n                  <jats:italic>c<\/jats:italic>\n                  -2 displays canonical thermostability and low-level peroxidase activity, while showing signs of elevated structural heterogeneity. These results reveal a new clade of eukaryotic cyt\n                  <jats:italic>c<\/jats:italic>\n                  variants with divergent biochemical properties and biological roles, opening new scaffolds for mechanistic discovery and redox engineering.\n                <\/jats:p>","DOI":"10.64898\/2025.12.23.696199","type":"posted-content","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T23:00:13Z","timestamp":1766703613000},"source":"Crossref","is-referenced-by-count":0,"title":["A Divergent Cytochrome c in Malaria Parasites with an Anomalously Low Redox Potential"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-6079","authenticated-orcid":false,"given":"Kade M.","family":"Loveridge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otessa D.","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel R.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7076-2145","authenticated-orcid":false,"given":"Tanya J.","family":"Espino-Sanchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7948-3241","authenticated-orcid":false,"given":"Henry","family":"Wienkers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-7740","authenticated-orcid":false,"given":"Christopher P.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Kay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3464-3042","authenticated-orcid":false,"given":"Paul A.","family":"Sigala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025122906100406000_2025.12.23.696199v1.1","doi-asserted-by":"publisher","DOI":"10.1021\/cr050241v"},{"key":"2025122906100406000_2025.12.23.696199v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.05.006"},{"key":"2025122906100406000_2025.12.23.696199v1.3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00257"},{"key":"2025122906100406000_2025.12.23.696199v1.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.46.070177.001503"},{"key":"2025122906100406000_2025.12.23.696199v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-024-01284-8"},{"key":"2025122906100406000_2025.12.23.696199v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13655"},{"key":"2025122906100406000_2025.12.23.696199v1.7","doi-asserted-by":"publisher","DOI":"10.1021\/cr0307143"},{"key":"2025122906100406000_2025.12.23.696199v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301047120"},{"key":"2025122906100406000_2025.12.23.696199v1.9","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.4c00450"},{"key":"2025122906100406000_2025.12.23.696199v1.10","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182013001674"},{"key":"2025122906100406000_2025.12.23.696199v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.168018"},{"key":"2025122906100406000_2025.12.23.696199v1.12","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.9b00735"},{"key":"2025122906100406000_2025.12.23.696199v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msaa015"},{"key":"2025122906100406000_2025.12.23.696199v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s007750050356"},{"key":"2025122906100406000_2025.12.23.696199v1.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1341-1"},{"key":"2025122906100406000_2025.12.23.696199v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"2025122906100406000_2025.12.23.696199v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21452"},{"key":"2025122906100406000_2025.12.23.696199v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.12.030"},{"issue":"24","key":"2025122906100406000_2025.12.23.696199v1.19","doi-asserted-by":"crossref","first-page":"11652","DOI":"10.1016\/S0021-9258(18)37834-7","article-title":"Cytochrome c: ion binding and redox properties. 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