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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Treatment:

Treatment ID:TR002044
Treatment Summary:Yeast strains with wild type or mutant histone H3 were cultured in yeast Synthetic Complete Medium before collection and extraction. As a control and for comparison, a strain with GSH1 deleted is included. GSH1 encodes for gamma glutamylcysteine synthetase, which catalyzes the first step in glutathione biosynthesis.
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