{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:49:23Z","timestamp":1790542163337,"version":"4.1.0"},"reference-count":190,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    The Apicomplexa phylum groups important human and animal pathogens that cause severe diseases, encompassing malaria, toxoplasmosis, and cryptosporidiosis. In common with most organisms, apicomplexans rely on heme as cofactor for several enzymes, including cytochromes of the electron transport chain. This heme derives from\n                    <jats:italic>de\u00a0novo<\/jats:italic>\n                    synthesis and\/or the development of uptake mechanisms to scavenge heme from their host. Recent studies have revealed that heme synthesis is essential for\n                    <jats:italic>Toxoplasma\u00a0gondii<\/jats:italic>\n                    tachyzoites, as well as for the mosquito and liver stages of\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    spp. In contrast, the erythrocytic stages of the malaria parasites rely on scavenging heme from the host red blood cell. The unusual heme synthesis pathway in Apicomplexa spans three cellular compartments and comprises enzymes of distinct ancestral origin, providing promising drug targets. Remarkably given the requirement for heme,\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    can tolerate the loss of several heme synthesis enzymes at a high fitness cost, while the ferrochelatase is essential for survival. These findings indicate that\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    is capable of salvaging heme precursors from its host. Furthermore, heme is implicated in the activation of the key antimalarial drug artemisinin. Recent findings established that a reduction in heme availability corresponds to decreased sensitivity to artemisinin in\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    and\n                    <jats:italic>Plasmodium\u00a0falciparum<\/jats:italic>\n                    , providing insights into the possible development of combination therapies to tackle apicomplexan parasites. This review describes the microeconomics of heme in Apicomplexa, from supply, either from\n                    <jats:italic>de\u00a0novo<\/jats:italic>\n                    synthesis or scavenging, to demand by metabolic pathways, including the electron transport chain.\n                  <\/jats:p>","DOI":"10.1111\/febs.15445","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T08:14:03Z","timestamp":1591949643000},"page":"382-404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Supply and demand\u2014heme synthesis, salvage and utilization by Apicomplexa"],"prefix":"10.1111","volume":"288","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-8599","authenticated-orcid":false,"given":"Joachim","family":"Kloehn","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Medicine CMU University of Geneva 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