CIAO3 protein forms a stable ternary complex with two key players of the human cytosolic iron–sulfur cluster assembly machinery

Maione, Vincenzo; Grifagni, Deborah; Torricella, Francesco; Cantini, Francesca; Banci, Lucia

doi:10.1007/s00775-020-01778-z

Cited by 11 publications

(9 citation statements)

References 38 publications

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“…CIAO3, which plays an essential role in bridging early and late CIA steps, has two Fe-S cluster binding sites: one at its N terminus and the other at its C terminus (28,29). Given that Fe-S clusters are intrinsically sensitive to the cellular environment and regulate the stability and/or function of Fe-S proteins, we reasoned that CIAO3 interactions may be regulated by its cluster incorporation status.…”

Section: Fe-s Cluster Incorporation Of Ciao3 Regulates Its Interactionsmentioning

confidence: 99%

“…Given that Fe-S clusters are intrinsically sensitive to the cellular environment and regulate the stability and/or function of Fe-S proteins, we reasoned that CIAO3 interactions may be regulated by its cluster incorporation status. Previous studies have indicated that missense mutations of CIAO3 substituting cysteine with serine at position 71 in the N terminus or at both positions 190 and 395 in the C terminus render the protein defective in binding of Fe-S clusters (28,29). Based on these studies, we generated CIAO3 mutants with impaired cluster incorporation (C71S, C190S/C395S, and C71S/C190S/C395S) to determine whether the Fe-S cluster requirement observed for CIAO3 interactions was dependent on cluster binding by CIAO3 itself (Fig.…”

Section: Fe-s Cluster Incorporation Of Ciao3 Regulates Its Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Iron-regulated assembly of the cytosolic iron–sulfur cluster biogenesis machinery

Fan¹,

Barshop²,

Vashisht³

et al. 2022

Journal of Biological Chemistry

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Section: Fe-s Cluster Incorporation Of Ciao3 Regulates Its Interactionsmentioning

confidence: 99%

Section: Fe-s Cluster Incorporation Of Ciao3 Regulates Its Interactionsmentioning

confidence: 99%

Iron-regulated assembly of the cytosolic iron–sulfur cluster biogenesis machinery

Fan¹,

Barshop²,

Vashisht³

et al. 2022

Journal of Biological Chemistry

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“…The [4Fe-4S] cluster is then presumably passed on via Nar1 to the CIA targeting complex (CTC) composed of Cia1-Cia2-Mms19 that mediate the maturation of target [4Fe-4S] proteins like DNA maintenance enzymes (11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…The CIA system initiates the synthesis of a [4Fe-4S] cluster on the cytosolic scaffold complex Cfd1-Nbp35, a reaction depending on the electron transport chain NADPH-Tah18-Dre2 (1, 10). The [4Fe-4S] cluster is then presumably passed on via Nar1 to the CIA targeting complex (CTC) composed of Cia1-Cia2-Mms19 that mediate the maturation of target [4Fe-4S] proteins like DNA maintenance enzymes (11–14).…”

Section: Introductionmentioning

confidence: 99%

Requirements for the Biogenesis of [2Fe-2S] Proteins in the Human and Yeast Cytosol

Braymer,

Stehling,

Stümpfig

et al. 2024

Preprint

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The biogenesis of iron-sulfur (Fe/S) proteins entails the synthesis and trafficking of Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, the multiple steps of biogenesis are accomplished by complex protein machineries in both mitochondria (ISC) and cytosol (CIA). The underlying biochemical pathways have been elucidated over the past decades, yet the mechanisms of cytosolic [2Fe-2S] protein assembly have remained ill-defined. Similarly, the precise site of glutathione (GSH) requirement in cytosolic and nuclear Fe/S protein biogenesis is unclear, as is the molecular role of the GSH-dependent cytosolic monothiol glutaredoxins (cGrxs). Here, we investigated these questions in human and yeast cells by various in vivo approaches. [2Fe-2S] cluster assembly of cytosolic target apoproteins required the mitochondrial ISC machinery, the ABC transporter Atm1/ABCB7 and GSH, yet occurred independently of both the CIA system and cGrxs. This mechanism was strikingly different from the ISC-, Atm1/ABCB7-, GSH-, and CIA-dependent assembly of cytosolic-nuclear [4Fe-4S] proteins. One notable exception to this newly defined cytosolic [2Fe-2S] protein maturation pathway was the yeast protein Apd1 which used the CIA system via binding to the CIA targeting complex through its C-terminal tryptophan. cGrxs, although attributed as [2Fe-2S] cluster chaperones or trafficking proteins, were not essential in vivo for delivering [2Fe-2S] clusters to either CIA components or apoproteins. Finally, GSH function was assigned to Atm1-dependent export, i.e. a step before GSH-dependent cGrxs function. Our findings extend the general model of eukaryotic Fe/S protein biogenesis by adding the molecular requirements for cytosolic [2Fe-2S] protein maturation.

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“…The CIA system initiates the synthesis of a [4Fe-4S] cluster on the cytosolic scaffold complex Cfd1-Nbp35, a reaction depending on the electron transport chain NADPH-Tah18-Dre2 ( 1 , 10 ). The [4Fe-4S] cluster is then presumably passed on via Nar1 to the CIA targeting complex (CTC) composed of Cia1-Cia2-Mms19 that mediate the maturation of target [4Fe-4S] proteins like DNA maintenance enzymes ( 11 – 14 ).…”

mentioning

confidence: 99%

Requirements for the biogenesis of [2Fe-2S] proteins in the human and yeast cytosol

Braymer,

Stehling,

Stümpfig

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The biogenesis of iron–sulfur (Fe/S) proteins entails the synthesis and trafficking of Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, the multiple steps of biogenesis are accomplished by complex protein machineries in both mitochondria and cytosol. The underlying biochemical pathways have been elucidated over the past decades, yet the mechanisms of cytosolic [2Fe-2S] protein assembly have remained ill-defined. Similarly, the precise site of glutathione (GSH) requirement in cytosolic and nuclear Fe/S protein biogenesis is unclear, as is the molecular role of the GSH-dependent cytosolic monothiol glutaredoxins (cGrxs). Here, we investigated these questions in human and yeast cells by various in vivo approaches. [2Fe-2S] cluster assembly of cytosolic target apoproteins required the mitochondrial ISC machinery, the mitochondrial transporter Atm1/ABCB7 and GSH, yet occurred independently of both the CIA system and cGrxs. This mechanism was strikingly different from the ISC-, Atm1/ABCB7-, GSH-, and CIA-dependent assembly of cytosolic–nuclear [4Fe-4S] proteins. One notable exception to this cytosolic [2Fe-2S] protein maturation pathway defined here was yeast Apd1 which used the CIA system via binding to the CIA targeting complex through its C-terminal tryptophan. cGrxs, although attributed as [2Fe-2S] cluster chaperones or trafficking proteins, were not essential in vivo for delivering [2Fe-2S] clusters to either CIA components or target apoproteins. Finally, the most critical GSH requirement was assigned to Atm1-dependent export, i.e. a step before GSH-dependent cGrxs function. Our findings extend the general model of eukaryotic Fe/S protein biogenesis by adding the molecular requirements for cytosolic [2Fe-2S] protein maturation.

show abstract

CIAO3 protein forms a stable ternary complex with two key players of the human cytosolic iron–sulfur cluster assembly machinery

Cited by 11 publications

References 38 publications

Iron-regulated assembly of the cytosolic iron–sulfur cluster biogenesis machinery

Iron-regulated assembly of the cytosolic iron–sulfur cluster biogenesis machinery

Requirements for the Biogenesis of [2Fe-2S] Proteins in the Human and Yeast Cytosol

Requirements for the biogenesis of [2Fe-2S] proteins in the human and yeast cytosol

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