Distinct roles for two N-terminal cleaved domains in mitochondrial import of the yeast frataxin homolog, Yfh1p

Donna M. Gordon, Mikhail Kogan, Simon A.B. Knight, Andrew Dancis, Debkumar Pain

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The yeast frataxin homolog (Yfh1p) participates in mitochondrial iron homeostasis. The phenotypic defects of the Δyfh1 mutant include drastic accumulation of iron in mitochondria and slow growth. The Yfh1p precursor protein contains two N-terminal domains that are sequentially cleaved by the matrix processing peptidase on import into mitochondria, generating the mature protein. We have precisely mapped these two cleavage sites. Mutations blocking the first or the second cleavage of Yfh1p do not interfere with its in vitro import or with its ability to complement phenotypes of the Δyfh1 mutant strain. Distinct roles have been ascertained for the two cleaved domains of Yfh1p. The first cleaved domain (domain I) is sufficient for in vitro mitochondrial import of a non-mitochondrial passenger protein. However, neither domain I nor other matrix-targeting signals alone can support efficient in vitro import of mature Yfh1p. The second cleaved domain (domain II) is required as a spacer between a targeting signal and mature Yfh1p. Likewise, when Yfb1p constructs lacking domain I or II are expressed in vivo, they fail to attain appreciable steady-state amounts in mitochondria and cannot complement phenotypes of the Δyfh1 mutant.

Original languageEnglish (US)
Pages (from-to)259-269
Number of pages11
JournalHuman molecular genetics
Volume10
Issue number3
DOIs
StatePublished - Feb 1 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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