{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:09:47Z","timestamp":1787065787663,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010293","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010225","name":"National Outstanding Youth Foundation of China","doi-asserted-by":"publisher","award":["31822054"],"award-info":[{"award-number":["31822054"]}],"id":[{"id":"10.13039\/501100010225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Many biosynthetic pathways produce pyrophosphate (PPi) as a by-product, which is cytotoxic if accumulated at high levels. Pyrophosphatases play pivotal roles in PPi detoxification by converting PPi to inorganic phosphate. A number of apicomplexan parasites, including\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    and\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    , express a PPi-dependent phosphofructokinase (PPi-PFK) that consumes PPi to power the phosphorylation of fructose-6-phosphate. However, the physiological roles of PPi-PFKs in these organisms are not known. Here, we report that\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    expresses both ATP- and PPi-dependent phosphofructokinases in the cytoplasm. Nonetheless, only PPi-PFK was indispensable for parasite growth, whereas the deletion of ATP-PFK did not affect parasite proliferation or virulence. The conditional depletion of PPi-PFK completely arrested parasite growth, but it did not affect the ATP level and only modestly reduced the flux of central carbon metabolism. However, PPi-PFK depletion caused a significant increase in cellular PPi and decreased the rates of nascent protein synthesis. The expression of a cytosolic pyrophosphatase in the PPi-PFK depletion mutant reduced its PPi level and increased the protein synthesis rate, therefore partially rescuing its growth. These results suggest that PPi-PFK has a major role in maintaining pyrophosphate homeostasis in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    . This role may allow PPi-PFK to fine-tune the balance of catabolism and anabolism and maximize the utilization efficiency for carbon nutrients derived from host cells, increasing the success of parasitism. Moreover, PPi-PFK is essential for parasite propagation and virulence\n                    <jats:italic>in vivo<\/jats:italic>\n                    but it is not present in human hosts, making it a potential drug target to combat toxoplasmosis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010293","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T13:32:15Z","timestamp":1643722335000},"page":"e1010293","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Essential role of pyrophosphate homeostasis mediated by the pyrophosphate-dependent phosphofructokinase in Toxoplasma gondii"],"prefix":"10.1371","volume":"18","author":[{"given":"Xuke","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-271X","authenticated-orcid":true,"given":"Bang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,1]]},"reference":[{"issue":"5","key":"ppat.1010293.ref001","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0020-711X(85)90288-5","article-title":"Inorganic pyrophosphate and inorganic pyrophosphatase in Escherichia coli","volume":"17","author":"E Kukko-Kalske","year":"1985","journal-title":"Int J Biochem"},{"key":"ppat.1010293.ref002","doi-asserted-by":"crossref","first-page":"110572","DOI":"10.1016\/j.plantsci.2020.110572","article-title":"Review: Crucial role of inorganic pyrophosphate in integrating carbon metabolism from sucrose breakdown to starch synthesis in rice endosperm","volume":"298","author":"SK Lee","year":"2020","journal-title":"Plant Sci"},{"issue":"Suppl 3","key":"ppat.1010293.ref003","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/1529-0131(197605\/06)19:3+<465::AID-ART1780190722>3.0.CO;2-#","article-title":"Metabolism of inorganic pyrophosphate (PPi).","volume":"19","author":"RG Russell","year":"1976","journal-title":"Arthritis Rheum"},{"issue":"2","key":"ppat.1010293.ref004","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1128\/mr.47.2.169-178.1983","article-title":"Microbial inorganic pyrophosphatases","volume":"47","author":"R. 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