Characterization of the apicoplast-localized enzyme TgUroD in Toxoplasma gondii reveals a key role of the apicoplast in heme biosynthesis
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Tjhin, Edwin; Hayward, Jenni; McFadden, Geoffrey I.; van Dooren, Giel
Description
Apicomplexan parasites such as Toxoplasma gondii possess an unusual heme biosynthesis pathway whose enzymes localize to the mitochondrion, cytosol, or apicoplast, a nonphotosynthetic plastid present in most apicomplexans. To characterize the involvement of the apicoplast in the T. gondii heme biosynthesis pathway, we investigated the role of the apicoplastlocalized enzyme uroporphyrinogen III decarboxylase (TgUroD). We found that TgUroD knockdown impaired parasite proliferation, decreased free...[Show more]
dc.contributor.author | Tjhin, Edwin | |
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dc.contributor.author | Hayward, Jenni | |
dc.contributor.author | McFadden, Geoffrey I. | |
dc.contributor.author | van Dooren, Giel | |
dc.date.accessioned | 2020-07-17T02:12:19Z | |
dc.identifier.issn | 0021-9258 | |
dc.identifier.uri | http://hdl.handle.net/1885/206330 | |
dc.description.abstract | Apicomplexan parasites such as Toxoplasma gondii possess an unusual heme biosynthesis pathway whose enzymes localize to the mitochondrion, cytosol, or apicoplast, a nonphotosynthetic plastid present in most apicomplexans. To characterize the involvement of the apicoplast in the T. gondii heme biosynthesis pathway, we investigated the role of the apicoplastlocalized enzyme uroporphyrinogen III decarboxylase (TgUroD). We found that TgUroD knockdown impaired parasite proliferation, decreased free heme levels in the parasite, and decreased the abundance of heme-containing c-type cytochrome proteins in the parasite mitochondrion. We validated the effects of heme loss on mitochondrial cytochromes by knocking down cytochrome c/c1 heme lyase 1 (TgCCHL1), a mitochondrial enzyme that catalyzes the covalent attachment of heme to c-type cytochromes. TgCCHL1 depletion reduced parasite proliferation and decreased the abundance of c-type cytochromes. We further sought to characterize the overall importance of TgUroD and TgCCHL1 for both mitochondrial and general parasite metabolism. TgUroD depletion decreased cellular ATP levels, mitochondrial oxygen consumption, and extracellular acidification rates. By contrast, depletion of TgCCHL1 neither diminished ATP levels in the parasite nor impaired extracellular acidification rate, but resulted in specific defects in mitochondrial oxygen consumption. Together, our results indicate that the apicoplast has a key role in heme biology in T. gondii and is important for both mitochondrial and general parasite metabolism. Our study highlights the importance of heme and its synthesis in these parasites. | |
dc.description.sponsorship | This work was supported by Australian Research Council (ARC) Discovery Project Grant DP110103144 (to G. G. v. D.) and the Research School of Biology Innovation Fund Grant (to G. G. v. D.). | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_AU | |
dc.publisher | American Society for Biochemistry and Molecular Biology Inc | |
dc.rights | © 2020 Tjhin et al. | |
dc.source | Journal of Biological Chemistry | |
dc.subject | Toxoplasma gondii | |
dc.subject | cytochrome | |
dc.subject | mitochondria | |
dc.subject | heme | |
dc.subject | electron transport | |
dc.subject | apicomplexa | |
dc.subject | apicoplast | |
dc.subject | cytochrome c/c1 heme lyase | |
dc.subject | heme biosynthesis | |
dc.subject | uroporphyrinogen III decarboxylase | |
dc.title | Characterization of the apicoplast-localized enzyme TgUroD in Toxoplasma gondii reveals a key role of the apicoplast in heme biosynthesis | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 295 | |
dc.date.issued | 2019-12-30 | |
local.identifier.absfor | 060107 - Enzymes | |
local.identifier.absfor | 060502 - Infectious Agents | |
local.identifier.absfor | 060104 - Cell Metabolism | |
local.identifier.ariespublication | u6269649xPUB748 | |
local.publisher.url | https://www.jbc.org/ | |
local.type.status | Accepted Version | |
local.contributor.affiliation | Tjhin, Edwin, Science; Health and Medicine (SHM), ANU | |
local.contributor.affiliation | Hayward, Jenni, College of Health and Medicine, ANU | |
local.contributor.affiliation | McFadden, Geoffrey I, University of Melbourne | |
local.contributor.affiliation | van Dooren, Giel, College of Science, ANU | |
dc.relation | http://purl.org/au-research/grants/arc/DP110103144 | |
local.bibliographicCitation.issue | 6 | |
local.bibliographicCitation.startpage | 1539 | |
local.bibliographicCitation.lastpage | 1550 | |
local.identifier.doi | 10.1074/jbc.RA119.011605 | |
local.identifier.absseo | 970106 - Expanding Knowledge in the Biological Sciences | |
local.identifier.absseo | 920109 - Infectious Diseases | |
dc.date.updated | 2020-04-05T08:19:56Z | |
local.identifier.scopusID | 2-s2.0-85079103146 | |
dcterms.accessRights | Open Access | |
dc.provenance | http://v2.sherpa.ac.uk/id/publication/10347..."Author accepted manuscript can be made open access on institutional repository" from SHERPA/RoMEO site (as at 17/7/20). | |
Collections | ANU Research Publications |
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File | Description | Size | Format | Image |
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Tjhin_et_al_2020.pdf | Author Accepted Manuscript | 3.07 MB | Adobe PDF |
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