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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.