Summary of Study ST001954

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001241. The data can be accessed directly via it's Project DOI: 10.21228/M89996 This work is supported by NIH grant, U2C- DK119886.

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Study IDST001954
Study TitleA pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich’s Ataxia
Study SummaryDisruptions to iron-sulfur (Fe-S) clusters, essential cofactors for a broad range of proteins, cause widespread cellular defects resulting in human disease. An underappreciated source of damage to Fe-S clusters are cuprous (Cu1+) ions. Since histone H3 enzymatically produces Cu1+ to support copper-dependent functions, we asked whether this activity could become detrimental to Fe-S clusters. Here, we report that histone H3-mediated Cu1+ toxicity is a major determinant of cellular functional pool of Fe-S clusters. Inadequate Fe-S cluster supply, either due to diminished assembly as occurs in Friedreich’s Ataxia or defective distribution, causes severe metabolic and growth defects in S. cerevisiae. Decreasing Cu1+ abundance, through attenuation of histone cupric reductase activity or depletion of total cellular copper, restored Fe-S cluster-dependent metabolism and growth. Our findings reveal a novel interplay between chromatin and mitochondria in Fe-S cluster homeostasis, and a potential pathogenic role for histone enzyme activity and Cu1+ in diseases with Fe-S cluster dysfunction.
Institute
University of California, Los Angeles
Last NameMatulionis
First NameNedas
Address615 Charles E Young Dr S, BSRB 354-05
Emailnmatulionis@mednet.ucla.edu
Phone3302346450
Submit Date2021-10-21
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2021-11-12
Release Version1
Nedas Matulionis Nedas Matulionis
https://dx.doi.org/10.21228/M89996
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Yeast; Subject species: Saccharomyces cerevisiae (Factor headings shown in green)

mb_sample_id local_sample_id Strain
SA184098cells-yeast-H3-dSGH1-01dGsh1
SA184099cells-yeast-H3-dSGH1-05dGsh1
SA184100cells-yeast-H3-dSGH1-03dGsh1
SA184101cells-yeast-H3-dSGH1-04dGsh1
SA184102cells-yeast-H3-dSGH1-02dGsh1
SA184088cells-yeast-H3-A110C-02H3A110C
SA184089cells-yeast-H3-A110C-05H3A110C
SA184090cells-yeast-H3-A110C-03H3A110C
SA184091cells-yeast-H3-A110C-04H3A110C
SA184092cells-yeast-H3-A110C-01H3A110C
SA184093cells-yeast-H3-H113N-05H3H113N
SA184094cells-yeast-H3-H113N-04H3H113N
SA184095cells-yeast-H3-H113N-03H3H113N
SA184096cells-yeast-H3-H113N-01H3H113N
SA184097cells-yeast-H3-H113N-02H3H113N
SA184103cells-yeast-WT-04wild type
SA184104cells-yeast-WT-01wild type
SA184105cells-yeast-WT-02wild type
SA184106cells-yeast-WT-05wild type
SA184107cells-yeast-WT-03wild type
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