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Copper transporters are responsible for copper isotopic fractionation in eukaryotic cells.

ABSTRACT: Copper isotopic composition is altered in cancerous compared to healthy tissues. However, the rationale for this difference is yet unknown. As a model of Cu isotopic fractionation, we monitored Cu uptake in Saccharomyces cerevisiae, whose Cu import is similar to human. Wild type cells are enriched in ⁶³Cu relative to ⁶⁵Cu. Likewise, ⁶³Cu isotope enrichment in cells without high-affinity Cu transporters is of slightly lower magnitude. In cells with compromised Cu reductase activity, however, no isotope fractionation is observed and when Cu is provided solely in reduced form for this strain, copper is enriched in ⁶³Cu like in the case of the wild type. Our results demonstrate that Cu isotope fractionation is generated by membrane importers and that its amplitude is modulated by Cu reduction. Based on ab initio calculations, we propose that the fractionation may be due to Cu binding with sulfur-rich amino acids: methionine and cysteine. In hepatocellular carcinoma (HCC), lower expression of the STEAP3 copper reductase and heavy Cu isotope enrichment have been reported for the tumor mass, relative to the surrounding tissue. Our study suggests that copper isotope fractionation observed in HCC could be due to lower reductase activity in the tumor.

SUBMITTER: Cadiou JL

PROVIDER: S-EPMC5356015 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Copper transporters are responsible for copper isotopic fractionation in eukaryotic cells.

Cadiou Jean-Loup JL Pichat Sylvain S Bondanese Victor P VP Soulard Alexandre A Fujii Toshiyuki T Albarède Francis F Oger Philippe P

Scientific reports 20170317

Copper isotopic composition is altered in cancerous compared to healthy tissues. However, the rationale for this difference is yet unknown. As a model of Cu isotopic fractionation, we monitored Cu uptake in Saccharomyces cerevisiae, whose Cu import is similar to human. Wild type cells are enriched in 63Cu relative to 65Cu. Likewise, 63Cu isotope enrichment in cells without high-affinity Cu transporters is of slightly lower magnitude. In cells with compromised Cu ...[more]

PMID: 28303916

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Project description:The chemical and isotopic signatures of moderately volatile elements are useful for understanding processes of volatile depletion in planetary formation and differentiation. However, the fractionation factors between gas and melt phases during evaporation that are required to model these planetary volatile depletion processes are still sparse. In this study, twenty heating experiments were conducted in 1 atm gas-mixing furnaces to constrain the behavior of K, Cu, and Zn evaporation and isotopic fractionation from basaltic melts at high temperatures. The temperatures range from 1300 °C to 1400 °C, and durations are from 2 to 8 days. Oxygen fugacities (fO2) range from one log unit below to ten log units above that of the iron-wüstite buffer (IW-1 to IW+10, corresponding to logfO2 of -10.7 to -0.68 at 1400 °C). The conditions were selected to achieve an evaporation-dominated regime (where timescales of diffusion << evaporation for trace elements) in order to avoid diffusion-limited evaporation. Our results show during evaporation Zn behaved as the most volatile, followed by Cu and then K, regardless of temperature and oxygen fugacity. Partitioning of Zn into spinel layers within experimental capsules, however, has been observed, which has substantial effects on the Zn isotope fractionation factor. Therefore, Zn results are presented but further discussion is excluded. Element loss depends on both temperature and oxygen fugacity, where higher temperatures and lower oxygen fugacities promote evaporation. However, with varying temperature and oxygen fugacity, the kinetic isotopic fractionation factors, α (where, RR0=fα-1 ), for K and Cu remain constant, thus these factors can be applied to a wider range of conditions than those in this study. The experimentally determined fractionation factors for K, and Cu during evaporation from basaltic melts are 0.9944, and 0.9961, respectively. The fractionation factors for these elements with varying volatilities are all significantly larger than the "apparent observed fractionation factors," which approach one and are inferred from lunar basalts relative to the Bulk Silicate Earth. This observation suggests near-equilibrium conditions during volatile-element loss from the Moon as the "apparent observed fractionation factors" of lunar basalts are similar for all three elements.

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Copper transporters are responsible for copper isotopic fractionation in eukaryotic cells.

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Copper transporters are responsible for copper isotopic fractionation in eukaryotic cells.

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