Ancestral roles of eukaryotic frataxin

Mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologues in trypanosomes

Shaojun Long, Milan Jirků, Jan Mach, Michael L. Ginger, Robert Sutak, Des Richardson, Jan Tachezy, Julius Lukeš

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Frataxin is a small conserved mitochondrial protein; in humans, mutations affecting frataxin expression or function result in Friedreich's ataxia. Much of the current understanding of frataxin function comes from informative studies with yeast models, but considerable debates remain with regard to the primary functions of this ubiquitous protein. We exploit the tractable reverse genetics of Trypanosoma brucei in order to specifically consider the importance of frataxin in an early branching lineage. Using inducible RNAi, we show that frataxin is essential in T. brucei and that its loss results in reduced activity of the marker Fe-S cluster-containing enzyme aconitase in both the mitochondrion and cytosol. Activities of mitochondrial succinate dehydrogenase and fumarase also decreased, but the concentration of reactive oxygen species increased. Trypanosomes lacking frataxin also exhibited a low mitochondrial membrane potential and reduced oxygen consumption. Crucially, however, iron did not accumulate in frataxin-depleted mitochondria, and as T. brucei frataxin does not form large complexes, it suggests that it plays no role in iron storage. Interestingly, RNAi phenotypes were ameliorated by expression of frataxin homologues from hydrogenosomes of another divergent protist Trichomonas vaginalis. Collectively, the data suggest trypanosome frataxin functions primarily only in Fe-S cluster biogenesis and protection from reactive oxygen species.

Original languageEnglish
Pages (from-to)94-109
Number of pages16
JournalMolecular Microbiology
Volume69
Issue number1
DOIs
Publication statusPublished - 1 Jul 2008
Externally publishedYes

Fingerprint

Trichomonas
Trypanosomiasis
Trypanosoma brucei brucei
RNA Interference
Reactive Oxygen Species
Mitochondria
Iron
Fumarate Hydratase
frataxin
Aconitate Hydratase
Friedreich Ataxia
Reverse Genetics
Trichomonas vaginalis
Succinate Dehydrogenase
Mitochondrial Membrane Potential
Mitochondrial Proteins
Oxygen Consumption
Cytosol
Yeasts

Cite this

Long, Shaojun ; Jirků, Milan ; Mach, Jan ; Ginger, Michael L. ; Sutak, Robert ; Richardson, Des ; Tachezy, Jan ; Lukeš, Julius. / Ancestral roles of eukaryotic frataxin : Mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologues in trypanosomes. In: Molecular Microbiology. 2008 ; Vol. 69, No. 1. pp. 94-109.
@article{2d199303696a44809aa9f944d67f711f,
title = "Ancestral roles of eukaryotic frataxin: Mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologues in trypanosomes",
abstract = "Frataxin is a small conserved mitochondrial protein; in humans, mutations affecting frataxin expression or function result in Friedreich's ataxia. Much of the current understanding of frataxin function comes from informative studies with yeast models, but considerable debates remain with regard to the primary functions of this ubiquitous protein. We exploit the tractable reverse genetics of Trypanosoma brucei in order to specifically consider the importance of frataxin in an early branching lineage. Using inducible RNAi, we show that frataxin is essential in T. brucei and that its loss results in reduced activity of the marker Fe-S cluster-containing enzyme aconitase in both the mitochondrion and cytosol. Activities of mitochondrial succinate dehydrogenase and fumarase also decreased, but the concentration of reactive oxygen species increased. Trypanosomes lacking frataxin also exhibited a low mitochondrial membrane potential and reduced oxygen consumption. Crucially, however, iron did not accumulate in frataxin-depleted mitochondria, and as T. brucei frataxin does not form large complexes, it suggests that it plays no role in iron storage. Interestingly, RNAi phenotypes were ameliorated by expression of frataxin homologues from hydrogenosomes of another divergent protist Trichomonas vaginalis. Collectively, the data suggest trypanosome frataxin functions primarily only in Fe-S cluster biogenesis and protection from reactive oxygen species.",
author = "Shaojun Long and Milan Jirků and Jan Mach and Ginger, {Michael L.} and Robert Sutak and Des Richardson and Jan Tachezy and Julius Lukeš",
year = "2008",
month = "7",
day = "1",
doi = "10.1111/j.1365-2958.2008.06260.x",
language = "English",
volume = "69",
pages = "94--109",
journal = "Molecular Microbiology",
issn = "0950-382X",
publisher = "Wiley-Blackwell",
number = "1",

}

Ancestral roles of eukaryotic frataxin : Mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologues in trypanosomes. / Long, Shaojun; Jirků, Milan; Mach, Jan; Ginger, Michael L.; Sutak, Robert; Richardson, Des; Tachezy, Jan; Lukeš, Julius.

In: Molecular Microbiology, Vol. 69, No. 1, 01.07.2008, p. 94-109.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ancestral roles of eukaryotic frataxin

T2 - Mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologues in trypanosomes

AU - Long, Shaojun

AU - Jirků, Milan

AU - Mach, Jan

AU - Ginger, Michael L.

AU - Sutak, Robert

AU - Richardson, Des

AU - Tachezy, Jan

AU - Lukeš, Julius

PY - 2008/7/1

Y1 - 2008/7/1

N2 - Frataxin is a small conserved mitochondrial protein; in humans, mutations affecting frataxin expression or function result in Friedreich's ataxia. Much of the current understanding of frataxin function comes from informative studies with yeast models, but considerable debates remain with regard to the primary functions of this ubiquitous protein. We exploit the tractable reverse genetics of Trypanosoma brucei in order to specifically consider the importance of frataxin in an early branching lineage. Using inducible RNAi, we show that frataxin is essential in T. brucei and that its loss results in reduced activity of the marker Fe-S cluster-containing enzyme aconitase in both the mitochondrion and cytosol. Activities of mitochondrial succinate dehydrogenase and fumarase also decreased, but the concentration of reactive oxygen species increased. Trypanosomes lacking frataxin also exhibited a low mitochondrial membrane potential and reduced oxygen consumption. Crucially, however, iron did not accumulate in frataxin-depleted mitochondria, and as T. brucei frataxin does not form large complexes, it suggests that it plays no role in iron storage. Interestingly, RNAi phenotypes were ameliorated by expression of frataxin homologues from hydrogenosomes of another divergent protist Trichomonas vaginalis. Collectively, the data suggest trypanosome frataxin functions primarily only in Fe-S cluster biogenesis and protection from reactive oxygen species.

AB - Frataxin is a small conserved mitochondrial protein; in humans, mutations affecting frataxin expression or function result in Friedreich's ataxia. Much of the current understanding of frataxin function comes from informative studies with yeast models, but considerable debates remain with regard to the primary functions of this ubiquitous protein. We exploit the tractable reverse genetics of Trypanosoma brucei in order to specifically consider the importance of frataxin in an early branching lineage. Using inducible RNAi, we show that frataxin is essential in T. brucei and that its loss results in reduced activity of the marker Fe-S cluster-containing enzyme aconitase in both the mitochondrion and cytosol. Activities of mitochondrial succinate dehydrogenase and fumarase also decreased, but the concentration of reactive oxygen species increased. Trypanosomes lacking frataxin also exhibited a low mitochondrial membrane potential and reduced oxygen consumption. Crucially, however, iron did not accumulate in frataxin-depleted mitochondria, and as T. brucei frataxin does not form large complexes, it suggests that it plays no role in iron storage. Interestingly, RNAi phenotypes were ameliorated by expression of frataxin homologues from hydrogenosomes of another divergent protist Trichomonas vaginalis. Collectively, the data suggest trypanosome frataxin functions primarily only in Fe-S cluster biogenesis and protection from reactive oxygen species.

UR - http://www.scopus.com/inward/record.url?scp=45149131789&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2958.2008.06260.x

DO - 10.1111/j.1365-2958.2008.06260.x

M3 - Article

VL - 69

SP - 94

EP - 109

JO - Molecular Microbiology

JF - Molecular Microbiology

SN - 0950-382X

IS - 1

ER -