{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:47:34Z","timestamp":1793242054373,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victoria University of Wellington Doctoral Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Feijoa is a rich source of bioactive compounds with anticancer, anti-inflammatory, antibacterial, and antifungal activities; however, the mechanism of action of these compounds is largely not known. Here, we used chemical genetic analyses in the model organism Saccharomyces cerevisiae to investigate the mechanism of action of a feijoa-derived ethanol adduct of vescalagin (EtOH-vescalagin). Genome-wide barcode sequencing analysis revealed yeast strains lacking genes in iron metabolism, zinc metabolism, retromer function, or mitochondrial function were hypersensitive to 0.3\u2005\u00b5M EtOH-vescalagin. This treatment increased expression of iron uptake proteins at the plasma membrane, which was a compensatory response to reduced intracellular iron. Likewise, EtOH-vescalagin increased expression of the Cot1 protein in the vacuolar membrane that transports zinc into the vacuole to prevent cytoplasmic accumulation of zinc. Each individual subunit in the retromer complex was required for the iron homeostatic mechanism of EtOH-vescalagin, while only the cargo recognition component in the retromer complex was required for the zinc homeostatic mechanism. Overexpression of either retromer subunits or high-affinity iron transporters suppressed EtOH-vescalagin bioactivity in a zinc-replete condition, while overexpression of only retromer subunits increased EtOH-vescalagin bioactivity in a zinc-deficient condition. Together, these results indicate that EtOH-vescalagin bioactivity begins with extracellular iron chelation and proceeds with intracellular transport of zinc via the retromer complex. More broadly, this is the first report of a bioactive compound to further characterize the poorly understood interaction between zinc metabolism and retromer function.<\/jats:p>","DOI":"10.1093\/g3journal\/jkae098","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T20:41:26Z","timestamp":1716928886000},"source":"Crossref","is-referenced-by-count":1,"title":["Chemical genomic analysis reveals the interplay between iron chelation, zinc homeostasis, and retromer function in the bioactivity of an ethanol adduct of the feijoa fruit\u2013derived ellagitannin vescalagin"],"prefix":"10.1093","volume":"14","author":[{"given":"Mona","family":"Mokhtari","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Victoria University of Wellington , Wellington 6012 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pegah","family":"Amiri","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Victoria University of Wellington , Wellington 6012 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darach","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University Medical School , Stanford, CA 94305 , USA"},{"name":"Department of Biology, Center for Genomics and Systems Biology, New York University , New York, NY 10003 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-0364","authenticated-orcid":false,"given":"David","family":"Gresham","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Genomics and Systems Biology, New York University , New York, NY 10003 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1936-5857","authenticated-orcid":false,"given":"Stephen J","family":"Bloor","sequence":"additional","affiliation":[{"name":"Callaghan Innovation , Lower Hutt 5040 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B","family":"Munkacsi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Victoria University of Wellington , Wellington 6012 , New Zealand"},{"name":"Centre for Biodiscovery, Victoria University of Wellington , Wellington 6012 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"issue":"9","key":"2024070811111230600_jkae098-B1","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1039\/c1mb05175j","article-title":"Secretory pathway genes assessed by high-throughput microscopy and synthetic genetic array analysis","volume":"7","author":"Bircham","year":"2011","journal-title":"Mol Biosyst"},{"issue":"20","key":"2024070811111230600_jkae098-B2","doi-asserted-by":"publisher","first-page":"3889","DOI":"10.1242\/jcs.00090","article-title":"Retromer function in endosome-to-Golgi 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