Plasmodium falciparum OTU‐like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8
Summary The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel ovarian tumour unit (OTU) domain‐containing cys...
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| Veröffentlicht in: | Cellular microbiology 2017-09, Vol.19 (9), p.e12748-n/a |
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| creator | Datta, Gaurav Hossain, Mohammad E. Asad, Mohd Rathore, Sumit Mohmmed, Asif |
| description | Summary
The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel ovarian tumour unit (OTU) domain‐containing cysteine protease of Plasmodium falciparum (PfOTU). A C‐terminal regulatable fluorescent affinity tag on native protein was utilised for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU and its association with the apicoplast. Degradation‐tag mediated knockdown of PfOTU resulted in abnormal apicoplast development and blocked development of parasites beyond early‐schizont stages in subsequent cell cycle; downregulation of PfOTU hindered apicoplast protein import. Further, the isoprenoid precursor‐mediated parasite growth‐rescue experiments confirmed that PfOTU knockdown specifically effect development of functional apicoplast. We also provide evidence for a possible biological function of PfOTU in membrane deconjugation of Atg8, which may be linked with the apicoplast protein import. Overall, our results show that the PfOTU is involved in apicoplast homeostasis and associates with the noncanonical function of Atg8 in maintenance of parasite apicoplast. |
| doi_str_mv | 10.1111/cmi.12748 |
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The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel ovarian tumour unit (OTU) domain‐containing cysteine protease of Plasmodium falciparum (PfOTU). A C‐terminal regulatable fluorescent affinity tag on native protein was utilised for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU and its association with the apicoplast. Degradation‐tag mediated knockdown of PfOTU resulted in abnormal apicoplast development and blocked development of parasites beyond early‐schizont stages in subsequent cell cycle; downregulation of PfOTU hindered apicoplast protein import. Further, the isoprenoid precursor‐mediated parasite growth‐rescue experiments confirmed that PfOTU knockdown specifically effect development of functional apicoplast. We also provide evidence for a possible biological function of PfOTU in membrane deconjugation of Atg8, which may be linked with the apicoplast protein import. Overall, our results show that the PfOTU is involved in apicoplast homeostasis and associates with the noncanonical function of Atg8 in maintenance of parasite apicoplast.</description><identifier>ISSN: 1462-5814</identifier><identifier>EISSN: 1462-5822</identifier><identifier>DOI: 10.1111/cmi.12748</identifier><identifier>PMID: 28423214</identifier><language>eng</language><publisher>England: Hindawi Limited</publisher><subject>Animals ; Animals, Genetically Modified - genetics ; apicoplast ; Apicoplasts - metabolism ; Autophagy-Related Protein 8 Family - metabolism ; autophagy‐linked protein Atg8 ; Cell cycle ; Cysteine ; Cysteine Proteases - genetics ; Cysteine Proteases - metabolism ; Cysteine proteinase ; Female ; Fluorescence ; Green Fluorescent Proteins - genetics ; Homeostasis ; Humans ; Imports ; Localization ; Maintenance ; malaria ; Malaria, Falciparum - parasitology ; Malaria, Falciparum - pathology ; Metabolic pathways ; Mice ; Mice, Inbred BALB C ; Mitochondria - metabolism ; Organelles ; OTU‐like protease ; Parasites ; Plasmodium ; Plasmodium falciparum ; Plasmodium falciparum - growth & development ; Protease ; Protein transport ; Protein Transport - genetics ; Proteins ; Protozoan Proteins - metabolism ; Rabbits ; regulatable fluorescent affinity tag ; Tumors</subject><ispartof>Cellular microbiology, 2017-09, Vol.19 (9), p.e12748-n/a</ispartof><rights>2017 John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3538-16a59c4f78f1172c7ad2ce8c05ca43b6ca63e745799042a763a79a984e85dc43</citedby><cites>FETCH-LOGICAL-c3538-16a59c4f78f1172c7ad2ce8c05ca43b6ca63e745799042a763a79a984e85dc43</cites><orcidid>0000-0002-0239-1979</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcmi.12748$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcmi.12748$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46387,46811</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28423214$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Datta, Gaurav</creatorcontrib><creatorcontrib>Hossain, Mohammad E.</creatorcontrib><creatorcontrib>Asad, Mohd</creatorcontrib><creatorcontrib>Rathore, Sumit</creatorcontrib><creatorcontrib>Mohmmed, Asif</creatorcontrib><title>Plasmodium falciparum OTU‐like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8</title><title>Cellular microbiology</title><addtitle>Cell Microbiol</addtitle><description>Summary
The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel ovarian tumour unit (OTU) domain‐containing cysteine protease of Plasmodium falciparum (PfOTU). A C‐terminal regulatable fluorescent affinity tag on native protein was utilised for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU and its association with the apicoplast. Degradation‐tag mediated knockdown of PfOTU resulted in abnormal apicoplast development and blocked development of parasites beyond early‐schizont stages in subsequent cell cycle; downregulation of PfOTU hindered apicoplast protein import. Further, the isoprenoid precursor‐mediated parasite growth‐rescue experiments confirmed that PfOTU knockdown specifically effect development of functional apicoplast. We also provide evidence for a possible biological function of PfOTU in membrane deconjugation of Atg8, which may be linked with the apicoplast protein import. Overall, our results show that the PfOTU is involved in apicoplast homeostasis and associates with the noncanonical function of Atg8 in maintenance of parasite apicoplast.</description><subject>Animals</subject><subject>Animals, Genetically Modified - genetics</subject><subject>apicoplast</subject><subject>Apicoplasts - metabolism</subject><subject>Autophagy-Related Protein 8 Family - metabolism</subject><subject>autophagy‐linked protein Atg8</subject><subject>Cell cycle</subject><subject>Cysteine</subject><subject>Cysteine Proteases - genetics</subject><subject>Cysteine Proteases - metabolism</subject><subject>Cysteine proteinase</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Imports</subject><subject>Localization</subject><subject>Maintenance</subject><subject>malaria</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Malaria, Falciparum - pathology</subject><subject>Metabolic pathways</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mitochondria - metabolism</subject><subject>Organelles</subject><subject>OTU‐like protease</subject><subject>Parasites</subject><subject>Plasmodium</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - growth & development</subject><subject>Protease</subject><subject>Protein transport</subject><subject>Protein Transport - genetics</subject><subject>Proteins</subject><subject>Protozoan Proteins - metabolism</subject><subject>Rabbits</subject><subject>regulatable fluorescent affinity tag</subject><subject>Tumors</subject><issn>1462-5814</issn><issn>1462-5822</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQhy0Eon_gwAsgS1zaw7a248TOsVoBrVTUHpazNXUm1CWJg8dRtTceoc_Ik-CypQckfBiPNJ8_jfVj7J0UJ7KcUz-GE6mMti_YvtSNWtVWqZfPvdR77IDoTgjZGClfsz1ltaqU1Pvs4XoAGmMXlpH3MPgwQyrt1ebrr58PQ_iO3G8pY5iQzylmBEJ-dN2X-TEPxJEIpxxg4H1MHObg41yEmd_GESNloALB1HEgij5ARuL3Id_yKU4eSgm-vE1xQB57fpa_2TfsVdmD8O3Tfcg2nz5u1uery6vPF-uzy5Wv6squZAN163VvbC-lUd5ApzxaL2oPurppPDQVGl2bthVagWkqMC20VqOtO6-rQ3a005Zf_ViQshsDeRwGmDAu5KRtpbCtaGRBP_yD3sUlTWU5J1tVW6G0eBQe7yifIlHC3s0pjJC2Tgr3mJIrKbk_KRX2_ZNxuRmxeyb_xlKA0x1wHwbc_t_k1l8udsrf07mdmg</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Datta, Gaurav</creator><creator>Hossain, Mohammad E.</creator><creator>Asad, Mohd</creator><creator>Rathore, Sumit</creator><creator>Mohmmed, Asif</creator><general>Hindawi Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0239-1979</orcidid></search><sort><creationdate>201709</creationdate><title>Plasmodium falciparum OTU‐like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8</title><author>Datta, Gaurav ; Hossain, Mohammad E. ; Asad, Mohd ; Rathore, Sumit ; Mohmmed, Asif</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-16a59c4f78f1172c7ad2ce8c05ca43b6ca63e745799042a763a79a984e85dc43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Animals, Genetically Modified - genetics</topic><topic>apicoplast</topic><topic>Apicoplasts - metabolism</topic><topic>Autophagy-Related Protein 8 Family - metabolism</topic><topic>autophagy‐linked protein Atg8</topic><topic>Cell cycle</topic><topic>Cysteine</topic><topic>Cysteine Proteases - genetics</topic><topic>Cysteine Proteases - metabolism</topic><topic>Cysteine proteinase</topic><topic>Female</topic><topic>Fluorescence</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Imports</topic><topic>Localization</topic><topic>Maintenance</topic><topic>malaria</topic><topic>Malaria, Falciparum - parasitology</topic><topic>Malaria, Falciparum - pathology</topic><topic>Metabolic pathways</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mitochondria - metabolism</topic><topic>Organelles</topic><topic>OTU‐like protease</topic><topic>Parasites</topic><topic>Plasmodium</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - growth & development</topic><topic>Protease</topic><topic>Protein transport</topic><topic>Protein Transport - genetics</topic><topic>Proteins</topic><topic>Protozoan Proteins - metabolism</topic><topic>Rabbits</topic><topic>regulatable fluorescent affinity tag</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Datta, Gaurav</creatorcontrib><creatorcontrib>Hossain, Mohammad E.</creatorcontrib><creatorcontrib>Asad, Mohd</creatorcontrib><creatorcontrib>Rathore, Sumit</creatorcontrib><creatorcontrib>Mohmmed, Asif</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cellular microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Datta, Gaurav</au><au>Hossain, Mohammad E.</au><au>Asad, Mohd</au><au>Rathore, Sumit</au><au>Mohmmed, Asif</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasmodium falciparum OTU‐like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8</atitle><jtitle>Cellular microbiology</jtitle><addtitle>Cell Microbiol</addtitle><date>2017-09</date><risdate>2017</risdate><volume>19</volume><issue>9</issue><spage>e12748</spage><epage>n/a</epage><pages>e12748-n/a</pages><issn>1462-5814</issn><eissn>1462-5822</eissn><abstract>Summary
The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel ovarian tumour unit (OTU) domain‐containing cysteine protease of Plasmodium falciparum (PfOTU). A C‐terminal regulatable fluorescent affinity tag on native protein was utilised for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU and its association with the apicoplast. Degradation‐tag mediated knockdown of PfOTU resulted in abnormal apicoplast development and blocked development of parasites beyond early‐schizont stages in subsequent cell cycle; downregulation of PfOTU hindered apicoplast protein import. Further, the isoprenoid precursor‐mediated parasite growth‐rescue experiments confirmed that PfOTU knockdown specifically effect development of functional apicoplast. We also provide evidence for a possible biological function of PfOTU in membrane deconjugation of Atg8, which may be linked with the apicoplast protein import. Overall, our results show that the PfOTU is involved in apicoplast homeostasis and associates with the noncanonical function of Atg8 in maintenance of parasite apicoplast.</abstract><cop>England</cop><pub>Hindawi Limited</pub><pmid>28423214</pmid><doi>10.1111/cmi.12748</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-0239-1979</orcidid></addata></record> |
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| subjects | Animals Animals, Genetically Modified - genetics apicoplast Apicoplasts - metabolism Autophagy-Related Protein 8 Family - metabolism autophagy‐linked protein Atg8 Cell cycle Cysteine Cysteine Proteases - genetics Cysteine Proteases - metabolism Cysteine proteinase Female Fluorescence Green Fluorescent Proteins - genetics Homeostasis Humans Imports Localization Maintenance malaria Malaria, Falciparum - parasitology Malaria, Falciparum - pathology Metabolic pathways Mice Mice, Inbred BALB C Mitochondria - metabolism Organelles OTU‐like protease Parasites Plasmodium Plasmodium falciparum Plasmodium falciparum - growth & development Protease Protein transport Protein Transport - genetics Proteins Protozoan Proteins - metabolism Rabbits regulatable fluorescent affinity tag Tumors |
| title | Plasmodium falciparum OTU‐like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8 |
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