Summary of project PR001241
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
| Project ID: | PR001241 |
| Project DOI: | doi: 10.21228/M89996 |
| Project Title: | A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich’s Ataxia |
| Project 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 |
| Department: | Biomedical Sciences |
| Last Name: | Matulionis |
| First Name: | Nedas |
| Address: | 615 Charles E Young Dr S, BSRB 354-05 |
| Email: | nmatulionis@mednet.ucla.edu |
| Phone: | 3302346450 |
Summary of all studies in project PR001241
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001954 | A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich’s Ataxia | Saccharomyces cerevisiae | University of California, Los Angeles | MS | 2021-11-12 | 1 | 20 | Uploaded data (1.1G)* |
