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Biogenesis of cellular iron-sulfur proteins: the essential role of mitochondria and the CIA machinery
Published on September 27, 2018 36 min
Other Talks in the Series: Mitochondria in Health and Disease
Hello, my name is Roland Lill. I'm a professor of Cell Biology at the Institute for Zytobiologie at the Phillips-University of Marburg in Germany. This is the second part of my lecture on the biogenesis of cellular iron-sulfur proteins in eukaryotes. In part one, I've explained the process inside mitochondria. Now, in part two, I will focus on our current knowledge of the assembly pathways of iron-sulfur proteins in the cytosol and nucleus.
Here is a brief outline of my lecture. I will first explain why the mitochondria and the related organelles called mitosomes are essential for biogenesis of cytosolic and nuclear iron-sulfur proteins, including some interesting evolutionary aspects. Then, I will provide you with an overview of how cytosolic and nuclear iron-sulfur proteins are matured. Then, I will explain our current functional views on some of the components involved in the biogenesis in more detail. Finally, I will outline the importance of iron-sulfur protein biogenesis for genome maintenance.
In the first part of this lecture series, I have explained how the mitochondrial ISC assembly machinery assists with the maturation of iron-sulfur proteins within this organelle. I also told you already that the core of the ISC system is involved in the biogenesis of cytosolic and nuclear iron-sulfur proteins, in that it synthesizes an unknown sulfur-containing molecule X-S that is exported to the cytosol via the ABC transporter Atm1. In the cytosol, to so-called CIA or cytosolic iron-sulfur protein assembly machinery catalyzes the process and the 11 known CIA components and the mechanisms of this machinery will be the main topic of this part two of my lecture. Let us now look at which important iron-sulfur proteins are located in the cytosol and nucleus, and here I can give you only a small selection of these proteins. A famous cytosolic iron-sulfur protein mentioned already in part one is the iron regulatory protein 1 in its aconitase form. Two proteins involved in various aspects of protein translation are Rli1, which helps to separate the ribosomal subunits after translation termination and Tyw1 which is involved in tRNA nucleotide modification. In the cell nucleus, many enzymes involved in DNA maintenance contain iron-sulfur clusters. We have reported in 2012 that the replicative DNA polymerases, for instance, deltas contain functionally important iron-sulfur clusters at their C-termini. Moreover, various ATP-dependent DNA helicases involved in DNA repair, telomere length regulation, and chromosome segregation and many other aspects have been shown to contain iron-sulfur clusters. Malfunction of these proteins due to an impaired iron-sulfur cluster insertion is associated with different aspects of genome stability, which will be explained later in my lecture. All of these letter iron-sulfur enzymes and many more, are essential for cell viability, for instance, of yeast cells. In turn, this is the reason why mitochondria are essential in the eukaryotic cell. You may now argue that mitochondria are essential because of their most popular role in respiration or oxidative phosphorylation. However, it is well-known that yeast cells can live without active respiration as long as glucose is present as a fermentable carbon source. Likewise, the late Giuseppe Attardi has shown in the 1990s that also, human cells can live without mitochondrial DNA and thus, without active respiration, as long as high glucose is applied to the cells. This is different for the mitochondrial ISC system where most of the core IC genes are essential for cell viability. The reason for this is their role in extramitochondrial and sulfur protein biogenesis. A nice biological confirmation of this concept is provided by biology itself and will be discussed in the next slide because it shows that this process can also be the minimal function of the organelles.