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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
Study ID | ST001954 |
Study Title | A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich’s Ataxia |
Study Summary | Disruptions 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 Name | Matulionis |
First Name | Nedas |
Address | 615 Charles E Young Dr S, BSRB 354-05 |
nmatulionis@mednet.ucla.edu | |
Phone | 3302346450 |
Submit Date | 2021-10-21 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2021-11-12 |
Release Version | 1 |
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Factors:
Subject type: Yeast; Subject species: Saccharomyces cerevisiae (Factor headings shown in green)
mb_sample_id | local_sample_id | Strain |
---|---|---|
SA184098 | cells-yeast-H3-dSGH1-01 | dGsh1 |
SA184099 | cells-yeast-H3-dSGH1-05 | dGsh1 |
SA184100 | cells-yeast-H3-dSGH1-03 | dGsh1 |
SA184101 | cells-yeast-H3-dSGH1-04 | dGsh1 |
SA184102 | cells-yeast-H3-dSGH1-02 | dGsh1 |
SA184088 | cells-yeast-H3-A110C-02 | H3A110C |
SA184089 | cells-yeast-H3-A110C-05 | H3A110C |
SA184090 | cells-yeast-H3-A110C-03 | H3A110C |
SA184091 | cells-yeast-H3-A110C-04 | H3A110C |
SA184092 | cells-yeast-H3-A110C-01 | H3A110C |
SA184093 | cells-yeast-H3-H113N-05 | H3H113N |
SA184094 | cells-yeast-H3-H113N-04 | H3H113N |
SA184095 | cells-yeast-H3-H113N-03 | H3H113N |
SA184096 | cells-yeast-H3-H113N-01 | H3H113N |
SA184097 | cells-yeast-H3-H113N-02 | H3H113N |
SA184103 | cells-yeast-WT-04 | wild type |
SA184104 | cells-yeast-WT-01 | wild type |
SA184105 | cells-yeast-WT-02 | wild type |
SA184106 | cells-yeast-WT-05 | wild type |
SA184107 | cells-yeast-WT-03 | wild type |
Showing results 1 to 20 of 20 |