PR001241 (Project)

Dcc Asset:

MW submission packet 20260310.zip

Processed File (Entity type)

Dcc:

Metabolomics

DCC (Entity type)

Child Project:

PPR00001

Project (Entity type)

Persistent Id:http://dx.doi.org/10.21228/M89996

Description: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.

Results found

Linked to

	Label	Description
	SU002032 Subject (Entity type)	A subject produced as part of the PR001241 project
	SA184107 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184089 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184097 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184095 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184096 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184102 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184094 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184099 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project
	SA184105 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001241 project