scholarly journals Frataxin-bypassing Isu1: characterization of the bypass activity in cells and mitochondria

2014 ◽  
Vol 459 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Heeyong Yoon ◽  
Simon A. B. Knight ◽  
Alok Pandey ◽  
Jayashree Pain ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Change ◽  
Scaffold Protein ◽  
Cluster Assembly ◽  
Cysteine Desulfurase ◽  
In Cells

The Fe–S cluster assembly scaffold protein Isu1 with the amino acid change M107I is able to bypass lack of the frataxin by stimulating cysteine desulfurase activity in mitochondria, although a kinetic defect in Fe–S cluster assembly persists.

scholarly journals Mutation in the Fe–S scaffold protein Isu bypasses frataxin deletion

2011 ◽  
Vol 441 (1) ◽  
pp. 473-480 ◽  
Author(s):  
Heeyong Yoon ◽  
Ramesh Golla ◽  
Emmanuel Lesuisse ◽  
Jayashree Pain ◽  
Jason E. Donald ◽  
...  
Keyword(s):  
Unique Feature ◽  
Mitochondrial Protein ◽  
Scaffold Protein ◽  
Yeast Cells ◽  
Single Amino Acid ◽  
Cluster Assembly ◽  
Iron Availability ◽  
Direct Effects ◽  
Cysteine Desulfurase ◽  
Mitochondrial Iron

Frataxin is a conserved mitochondrial protein deficient in patients with Friedreich's ataxia. Frataxin has been implicated in control of iron homoeostasis and Fe–S cluster assembly. In yeast or human mitochondria, frataxin interacts with components of the Fe–S cluster synthesis machinery, including the cysteine desulfurase Nfs1, accessory protein Isd11 and scaffold protein Isu. In the present paper, we report that a single amino acid substitution (methionine to isoleucine) at position 107 in the mature form of Isu1 restored many deficient functions in Δyfh1 or frataxin-depleted yeast cells. Iron homoeostasis was improved such that soluble/usable mitochondrial iron was increased and accumulation of insoluble/non-usable iron within mitochondria was largely prevented. Cytochromes were returned to normal and haem synthesis was restored. In mitochondria carrying the mutant Isu1 and no frataxin, Fe–S cluster enzyme activities were improved. The efficiency of new Fe–S cluster synthesis in isolated mitochondria was markedly increased compared with frataxin-negative cells, although the response to added iron was minimal. The M107I substitution in the highly conserved Isu scaffold protein is typically found in bacterial orthologues, suggesting that a unique feature of the bacterial Fe–S cluster machinery may be involved. The mechanism by which the mutant Isu bypasses the absence of frataxin remains to be determined, but could be related to direct effects on Fe–S cluster assembly and/or indirect effects on mitochondrial iron availability.

scholarly journals Mitochondrial and Nucleolar Localization of Cysteine Desulfurase Nfs and the Scaffold Protein Isu in Trypanosoma brucei

2013 ◽  
Vol 13 (3) ◽  
pp. 353-362 ◽  
Author(s):  
Julie Kovářová ◽  
Eva Horáková ◽  
Piya Changmai ◽  
Marie Vancová ◽  
Julius Lukeš
Keyword(s):  
Trypanosoma Brucei ◽  
Morphological Changes ◽  
Scaffold Protein ◽  
Complex Life Cycle ◽  
Insect Vector ◽  
Cluster Assembly ◽  
Cysteine Desulfurase ◽  
Content Type ◽  
Dual Localization ◽  
Localization Signal

ABSTRACT Trypanosoma brucei has a complex life cycle during which its single mitochondrion is subjected to major metabolic and morphological changes. While the procyclic stage (PS) of the insect vector contains a large and reticulated mitochondrion, its counterpart in the bloodstream stage (BS) parasitizing mammals is highly reduced and seems to be devoid of most functions. We show here that key Fe-S cluster assembly proteins are still present and active in this organelle and that produced clusters are incorporated into overexpressed enzymes. Importantly, the cysteine desulfurase Nfs, equipped with the nuclear localization signal, was detected in the nucleolus of both T. brucei life stages. The scaffold protein Isu, an interacting partner of Nfs, was also found to have a dual localization in the mitochondrion and the nucleolus, while frataxin and both ferredoxins are confined to the mitochondrion. Moreover, upon depletion of Isu, cytosolic tRNA thiolation dropped in the PS but not BS parasites.

scholarly journals Overlapping Binding Sites of the Frataxin Homologue Assembly Factor and the Heat Shock Protein 70 Transfer Factor on the Isu Iron-Sulfur Cluster Scaffold Protein

2014 ◽  
Vol 289 (44) ◽  
pp. 30268-30278 ◽  
Author(s):  
Mateusz Manicki ◽  
Julia Majewska ◽  
Szymon Ciesielski ◽  
Brenda Schilke ◽  
Anna Blenska ◽  
...  
Keyword(s):  
Transfer Factor ◽  
Binding Sites ◽  
Scaffold Protein ◽  
Sequence Motif ◽  
Cluster Assembly ◽  
Assembly Process ◽  
Cysteine Desulfurase ◽  
Iron Sulfur Cluster ◽  
Cluster Transfer ◽  
Assembly Factor

In mitochondria FeS clusters, prosthetic groups critical for the activity of many proteins, are first assembled on Isu, a 14-kDa scaffold protein, and then transferred to recipient apoproteins. The assembly process involves interaction of Isu with both Nfs1, the cysteine desulfurase serving as a sulfur donor, and the yeast frataxin homolog (Yfh1) serving as a regulator of desulfurase activity and/or iron donor. Here, based on the results of biochemical experiments with purified wild-type and variant proteins, we report that interaction of Yfh1 with both Nfs1 and Isu are required for formation of a stable tripartite assembly complex. Disruption of either Yfh1-Isu or Nfs1-Isu interactions destabilizes the complex. Cluster transfer to recipient apoprotein is known to require the interaction of Isu with the J-protein/Hsp70 molecular chaperone pair, Jac1 and Ssq1. Here we show that the Yfh1 interaction with Isu involves the PVK sequence motif, which is also the site key for the interaction of Isu with Hsp70 Ssq1. Coupled with our previous observation that Nfs1 and Jac1 binding to Isu is mutually exclusive due to partially overlapping binding sites, we propose that such mutual exclusivity of cluster assembly factor (Nfs1/Yfh1) and cluster transfer factor (Jac1/Ssq1) binding to Isu has functional consequences for the transition from the assembly process to the transfer process, and thus regulation of the biogenesis of FeS cluster proteins.

Structural and functional characterization of an iron–sulfur cluster assembly scaffold protein-SufA from Plasmodium vivax

Gene ◽  
2016 ◽  
Vol 585 (1) ◽  
pp. 159-165 ◽  
Author(s):  
Zarna Rajeshkumar Pala ◽  
Vishal Saxena ◽  
Gagandeep Singh Saggu ◽  
Sushil Kumar Yadav ◽  
R.P. Pareek ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Functional Characterization ◽  
Scaffold Protein ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur

Characterization of the amino acid change in a transferrin variant

1988 ◽  
Vol 16 (5) ◽  
pp. 834-835 ◽  
Author(s):  
ROBERT W. EVANS ◽  
ANDREW MEILAK ◽  
ALASTAIR AITKEN ◽  
KOKILA J. PATEL ◽  
COLLIN WONG ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Change

scholarly journals A missed Fe-S cluster handoff causes a metabolic shakeup

2018 ◽  
Vol 293 (21) ◽  
pp. 8312-8313 ◽  
Author(s):  
Olivier Berteau
Keyword(s):  
Human Disease ◽  
Lipid Droplets ◽  
General Framework ◽  
Scaffold Protein ◽  
Cellular System ◽  
Metabolic Reprogramming ◽  
Cluster Assembly ◽  
Iron Sulfur ◽  
Pathological Conditions ◽  
In Cells

The general framework of pathways by which iron–sulfur (Fe-S) clusters are assembled in cells is well-known, but the cellular consequences of disruptions to that framework are not fully understood. Crooks et al. report a novel cellular system that creates an acute Fe-S cluster deficiency, using mutants of ISCU, the main scaffold protein for Fe-S cluster assembly. Surprisingly, the resultant metabolic reprogramming leads to the accumulation of lipid droplets, a situation encountered in many poorly understood pathological conditions, highlighting unanticipated links between Fe-S assembly machinery and human disease.

Sign in / Sign up

Export Citation Format

Share Document