Posttranslational regulation of the scaffold for Fe-S cluster biogenesis, Isu.
Isu, the scaffold protein on which Fe-S clusters are built in the mitochondrial matrix, plays a central role in the biogenesis of Fe-S cluster proteins. We report that the reduction in the activity of several components of the cluster biogenesis system, including the specialized Hsp70 Ssq1, causes a 15-20-fold up-regulation of Isu. This up-regulation results from changes at both the transcriptional and posttranslational level: an increase in ISU mRNA levels and in stability of ISU protein. Its biological importance is demonstrated by the fact that cells lacking Ssq1 grow poorly when Isu levels are prevented from rising above those found in wild-type cells. Of the biogenesis factors tested, Nfs1, the sulfur donor, was unique. Little increase in Isu levels occurred when Nfs1 was depleted. However, its presence was required for the up-regulation caused by reduction in activity of other components. Our results are consistent with the existence of a mechanism to increase the stability of Isu, and thus its level, that is dependent on the presence of the cysteine desulfurase Nfs1.
Andrew
Amy J
AJ
Department of Biochemistry, University of Wisconsin, Madison WI 53706, USA.
Song
Ji-Yoon
JY
Schilke
Brenda
B
Craig
Elizabeth A
EA
D015966:Gene Expression Regulation, Fungal; D018840:HSP70 Heat-Shock Proteins; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013466:Sulfurtransferases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C090297:AFT1 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; C121520:ISU1 protein, S cerevisiae; C121521:ISU2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C115913:SSQ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D013466:Sulfurtransferases; C115912:NFS1 protein, S cerevisiae