GTP is required for iron-sulfur cluster biogenesis in mitochondria

Boominathan Amutha, Donna M. Gordon, Yajuan Gu, Elise R. Lyver, Andrew Dancis, Debkumar Pain

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Iron-sulfur (Fe-S) cluster biogenesis in mitochondria is an essential process and is conserved from yeast to humans. Several proteins with Fe-S cluster cofactors reside in mitochondria, including aconitase [4Fe-4S] and ferredoxin [2Fe-2S]. We found that mitochondria isolated from wild-type yeast contain a pool of apoaconitase and machinery capable of forming new clusters and inserting them into this endogenous apoprotein pool. These observations allowed us to develop assays to assess the role of nucleotides (GTP and ATP) in cluster biogenesis in mitochondria. We show that Fe-S cluster biogenesis in isolated mitochondria is enhanced by the addition of GTP and ATP. Hydrolysis of both GTP and ATP is necessary, and the addition of ATP cannot circumvent processes that require GTP hydrolysis. Both in vivo and in vitro experiments suggest that GTP must enter into the matrix to exert its effects on cluster biogenesis. Upon import into isolated mitochondria, purified apoferredoxin can also be used as a substrate by the Fe-S cluster machinery in a GTP-dependent manner. GTP is likely required for a common step involved in the cluster biogenesis of aconitase and ferredoxin. To our knowledge this is the first report demonstrating a role of GTP in mitochondrial Fe-S cluster biogenesis.

Original languageEnglish (US)
Pages (from-to)1362-1371
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number3
DOIs
StatePublished - Jan 18 2008

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Mitochondria
Guanosine Triphosphate
Sulfur
Iron
Adenosine Triphosphate
Aconitate Hydratase
Yeast
Machinery
Hydrolysis
Yeasts
Ferredoxins
Apoproteins
Assays
Nucleotides
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Amutha, Boominathan ; Gordon, Donna M. ; Gu, Yajuan ; Lyver, Elise R. ; Dancis, Andrew ; Pain, Debkumar. / GTP is required for iron-sulfur cluster biogenesis in mitochondria. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 3. pp. 1362-1371.
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GTP is required for iron-sulfur cluster biogenesis in mitochondria. / Amutha, Boominathan; Gordon, Donna M.; Gu, Yajuan; Lyver, Elise R.; Dancis, Andrew; Pain, Debkumar.

In: Journal of Biological Chemistry, Vol. 283, No. 3, 18.01.2008, p. 1362-1371.

Research output: Contribution to journalArticle

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