Summary of project PR001241

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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

Summary of all studies in project PR001241

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : 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)*