A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich's ataxia

被引：13

作者：

Campos, Oscar A. ^{[1
,2
]}

Attar, Narsis ^{[1
,2
]}

Cheng, Chen ^{[1
]}

Vogelauer, Maria ^{[1
]}

Mallipeddi, Nathan, V ^{[1
]}

Schmollinger, Stefan ^{[3
]}

Matulionis, Nedas ^{[1
]}

Christofk, Heather R. ^{[1
,2
,4
]}

Merchant, Sabeeha S. ^{[3
,5
,6
]}

Kurdistani, Siavash K. ^{[1
,2
,4
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA

[3] Univ Calif Berkeley, QB3 Berkeley, Berkeley, CA 94720 USA

[4] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, David Geffen Sch Med, Los Angeles, CA 90095 USA

[5] Univ Calif Berkeley, Dept Mol & Cell Biol & Plant, Berkeley, CA 94720 USA

[6] Lawrence Berkeley Natl Lab, Environm Genom & Syst Biol, Berkeley, CA 94720 USA

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 51期

关键词：

IRON-SULFUR CLUSTER; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; 4FE-4S CLUSTER; PROTEIN; GENE; BIOGENESIS; ACONITASE; MATURATION; BIOSYNTHESIS;

D O I：

10.1126/sciadv.abj9889

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Disruptions to iron-sulfur (Fe-S) clusters, essential cofactors for a broad range of proteins, cause widespread cellular defects resulting in human disease. A source of damage to Fe-S clusters is cuprous (Cu1+) ions. Since histone H3 enzymatically produces Cu1+ for 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, due to diminished assembly as occurs in Friedreich's ataxia or defective distribution, causes severe metabolic and growth defects in Saccharomyces 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 an 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.

引用

页数：11

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