Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis

Rutherford, Julian C.; Ojeda, Luis; Balk, Janneke; Mühlenhoff, Ulrich; Lill, Roland; Winge, Dennis R.

doi:10.1074/jbc.m413731200

Cited by 216 publications

(259 citation statements)

References 34 publications

Supporting

Mentioning

248

Contrasting

Unclassified

Order By: Relevance

“…The iron regulon is transcriptionally activated in response to iron deprivation by the iron-dependent transcription factors Aft1/2p (Rutherford et al, 2005). Despite the constitutive up-regulation of iron uptake genes, Aft1p was not constitutively activated in isc1⌬ mutants.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, Isc1p deficiency significantly increased Aft1p activation upon iron chelation. Aft1p functions as an iron sensor responding to a signal connected to mitochondrial ironsulfur cluster biogenesis (Rutherford et al, 2005). The identification of this signal and whether it increases to higher levels in iron depleted isc1⌬ cells is an important issue for future studies.…”

Section: Discussionmentioning

confidence: 99%

“…The Aft1p transcription factor is a key regulator of the iron regulon (Rutherford et al, 2005). Under iron-sufficient conditions, Aft1p remains inactive because of its cytoplasmic localization.…”

Section: Isc1p Deficiency Increase Iron Levelsmentioning

confidence: 99%

See 2 more Smart Citations

Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis

Almeida

Marques

Mojžita

et al. 2008

MBoC

109

View full text Add to dashboard Cite

The inositolphosphosphingolipid phospholipase C (Isc1p) of Saccharomyces cerevisiae belongs to the family of neutral sphingomyelinases that generates the bioactive sphingolipid ceramide. In this work the role of Isc1p in oxidative stress resistance and chronological lifespan was investigated. Loss of Isc1p resulted in a higher sensitivity to hydrogen peroxide that was associated with an increase in oxidative stress markers, namely intracellular oxidation, protein carbonylation, and lipid peroxidation. Microarray analysis showed that Isc1p deficiency up-regulated the iron regulon leading to increased levels of iron, which is known to catalyze the production of the highly reactive hydroxyl radicals via the Fenton reaction. In agreement, iron chelation suppressed hydrogen peroxide sensitivity of isc1⌬ mutants. Cells lacking Isc1p also displayed a shortened chronological lifespan associated with oxidative stress markers and aging of parental cells was correlated with a decrease in Isc1p activity. The analysis of DNA fragmentation and caspase-like activity showed that Isc1p deficiency increased apoptotic cell death associated with oxidative stress and aging. Furthermore, deletion of Yca1p metacaspase suppressed the oxidative stress sensitivity and premature aging phenotypes of isc1⌬ mutants. These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis

Almeida

Marques

Mojžita

et al. 2008

MBoC

109

View full text Add to dashboard Cite

show abstract

“…However, Aft1 iron sensing does not require the cytoplasmic machinery to mature Fe-S clusters (Rutherford et al 2005), demonstrating that iron sensing by Aft1 is not linked to the maturation of cytosolic 4Fe-4S clusters.…”

Section: Metal Ion Pools Within Mitochondriamentioning

confidence: 94%

“…Iron sensing by Aft1 requires proper mitochondrial Fe-S cluster biosynthesis, as well as the export of an ill-defined intermediate through the Atm1 IM transporter (Rutherford et al 2005). However, Aft1 iron sensing does not require the cytoplasmic machinery to mature Fe-S clusters (Rutherford et al 2005), demonstrating that iron sensing by Aft1 is not linked to the maturation of cytosolic 4Fe-4S clusters.…”

Section: Metal Ion Pools Within Mitochondriamentioning

confidence: 99%

Metal Ion availability in mitochondria

2007

Self Cite

View full text Add to dashboard Cite

Mitochondrial [2Fe‐2S] ferredoxins: new functions for old dogs

et al. 2022

Self Cite

View full text Add to dashboard Cite

Ferredoxins (FDXs) comprise a large family of iron–sulfur proteins that shuttle electrons from NADPH and FDX reductases into diverse biological processes. This review focuses on the structure, function and specificity of mitochondrial [2Fe‐2S] FDXs that are related to bacterial FDXs due to their endosymbiotic inheritance. Their classical function in cytochrome P450‐dependent steroid transformations was identified around 1960, and is exemplified by mammalian FDX1 (aka adrenodoxin). Thirty years later the essential function in cellular Fe/S protein biogenesis was discovered for the yeast mitochondrial FDX Yah1 that is additionally crucial for the formation of haem a and ubiquinone CoQ6. In mammals, Fe/S protein biogenesis is exclusively performed by the FDX1 paralog FDX2, despite the high structural similarity of both proteins. Recently, additional and specific roles of human FDX1 in haem a and lipoyl cofactor biosyntheses were described. For lipoyl synthesis, FDX1 transfers electrons to the radical S‐adenosyl methionine‐dependent lipoyl synthase to kickstart its radical chain reaction. The high target specificity of the two mammalian FDXs is contained within small conserved sequence motifs, that upon swapping change the target selection of these electron donors.

show abstract

Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis

Cited by 216 publications

References 34 publications

Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis

Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis

Metal Ion availability in mitochondria

Mitochondrial [2Fe‐2S] ferredoxins: new functions for old dogs

Contact Info

Product

Resources

About