Role of Nfu1 and Bol3 in iron-sulfur cluster transfer to mitochondrial clients
Abstract
Iron-sulfur (Fe-S) clusters are essential for many cellular processes, ranging from aerobic respiration, metabolite biosynthesis, ribosome assembly and DNA repair. Mutations in NFU1 and BOLA3 have been linked to genetic diseases with defects in mitochondrial Fe-S centers. Through genetic studies in yeast, we demonstrate that Nfu1 functions in a late step of [4Fe-4S] cluster biogenesis that is of heightened importance during oxidative metabolism. Proteomic studies revealed Nfu1 physical interacts with components of the ISA [4Fe-4S] assembly complex and client proteins that need [4Fe-4S] clusters to function. Additional studies focused on the mitochondrial BolA proteins, Bol1 and Bol3 (yeast homolog to human BOLA3), revealing that Bol1 functions earlier in Fe-S biogenesis with the monothiol glutaredoxin, Grx5, and Bol3 functions late with Nfu1. Given these observations, we propose that Nfu1, assisted by Bol3, functions to facilitate Fe-S transfer from the biosynthetic apparatus to the client proteins preventing oxidative damage to [4Fe-4S] clusters.
Article and author information
Author details
Funding
National Institutes of Health (RO1 GM110755)
- Dennis R Winge
National Institutes of Health (R01 GM112763)
- James A Wohlschlegel
National Institutes of Health (T32 DK007115)
- Andrew Melber
Deutsche Forschungsgemeinschaft (SPP 1710)
- Roland Lill
Deutsche Forschungsgemeinschaft (Spp 1927)
- Roland Lill
National Institutes of Health (P30 CA042014)
- Dennis R Winge
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Nikolaus Pfanner, University of Freiburg, Germany
Version history
- Received: March 11, 2016
- Accepted: August 16, 2016
- Accepted Manuscript published: August 17, 2016 (version 1)
- Version of Record published: September 7, 2016 (version 2)
Copyright
© 2016, Melber et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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