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Copper is a redox-active antimicrobial metal that can become increasingly toxic depending on the target biomolecule\u2019s donor atom selectivity and the chemical species of copper present. Mass is the traditional measurement of the intrinsic elemental chemistry, but this practice fails to reflect the morphology and surface area reactivity of nanotechnology. The carboxymethyl cellulose copper nanoparticles (CMC-Cu) investigated in this study have unique and undefined toxicity to Saccharomyces cerevisiae that is different from CuSO4. Cellular surface damage was found in scanning electron micrographs upon CMC-Cu exposure. Further investigation into the lipids revealed altered phosphatidylcholine and phosphatidylethanolamine membrane composition, as well as depleted triacylglycerols, suggesting an impact on the Kennedy lipid pathway. High levels of reactive oxygen species were measured which likely played a role in the lipid peroxidation detected with CMC-Cu treatment. Metal homeostasis was affected by CMC-Cu treatment. The copper sensitive yeast strain, YJM789, significantly decreased cellular zinc concentrations while the copper concentrations increased, suggesting a possible ionic mimicry relationship. In contrast to other compounds that generate ROS, no evidence of genotoxicity was found. As commonplace objects become more integrated with nanotechnology, humanity must look forward past traditional measurements of toxicity.<\/jats:p>","DOI":"10.1039\/d0mt00018c","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T12:14:50Z","timestamp":1585829690000},"page":"799-812","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Metallomic and lipidomic analysis of <i>S. cerevisiae<\/i> response to cellulosic copper nanoparticles uncovers drivers of toxicity"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-0594","authenticated-orcid":false,"given":"Matthew J","family":"Winans","sequence":"first","affiliation":[{"name":"West Virginia University \u2013 Biology Department, 53 Campus Drive LSB 3140, Morgantown, WV, 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6163-3181","authenticated-orcid":false,"given":"Jennifer E G","family":"Gallagher","sequence":"additional","affiliation":[{"name":"West Virginia University \u2013 Biology Department, 53 Campus Drive LSB 3140, Morgantown, WV, 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"2021121023194202600_cit1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1177\/1528083706060785","volume":"35","author":"Gabbay","year":"2006","journal-title":"J. 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