Fe-S Cluster Synthesis in A Eukaryote Without ISC Pathway
Normally, it was known that all eukaryotes have mitochondria or at least present some mitochondria-related organelles. With the discovering of Monocercomonoides, this known fact is not that true anymore. Monocercomonoides are flagellates in order oxymonad and lives in the digestive tracts of animals. Many kinds of research show that there is no observation of any mitochondria-related organelle or protein under the electron microscope1. That makes this genus is the first discovered eukaryotic organism that completely lacks any mitochondria2.
There are lots of essential processes in mitochondria that all the eukaryotes need to perform. One of these processes is called Fe-S cluster synthesis. These Fe-S cluster proteins are important because they have essential roles in cellular reactions. For instance, electron transport, enzyme catalysis, or some DNA processes like transcription or translation3. In this scenario, this flagellate organism has a different pathway to synthesis, but how? Normally, eukaryotes have a pathway for Fe-S cluster synthesis which is called mitochondrial iron-sulfur cluster (ISC) which is mentioned below in figure4.
In the figure, it is observed that the biogenesis of Fe-S proteins starts at mitochondrial ISC and is finished at cytosol with cytosolic Fe-S cluster assembly system (CIA). Despite its complicated biogenesis, the CIA system is specialized for eukaryotes and dependent on the ISC system5. After the synthesis, these proteins carry out their functions in the nucleus, cytosol, and mitochondria6. ISC pathway is essential and an important part of mitochondria, but genes that encode proteins for the ISC pathway cannot be found in Monocercomonoides just like the mitochondria itself2. That means Monocercomonoides do not have an ISC pathway, but somehow show the CIA pathway5. So how they can create Fe-S clusters without mitochondria and the ISC system?
Eventually, it was observed that Monocercomonoides have some proteins that are normally found in the sulfur mobilization system (SUF) that functions in the cytosol. SUF is one of the pathways that prokaryotes use for Fe-S cluster synthesis5. That means, this genus replaced the ISC system with the SUF system for Fe-S cluster synthesis. When compared with the prokaryotic SUF pathway, Monocercomonoides have a reduced version of this system. It is because of the absence of some SUF proteins because they only contain a few of them.
This leads to a final question, how exactly this system acquired? The reason behind this mitochondria loss and changing the system of the Fe-S cluster system have a hypothesize that it is a secondary loss. That is mainly because it is being accepted that all eukaryotes have a common ancestor (FIG. 3), which leads to the thought of previously existed oxymonads had mitochondria before2. It is been thought that the SUF system is obtained from a eubacterium by horizontal gene transfer (HGT)5. It is a known fact that there is a high frequency of prokaryote-to-prokaryote HGT7. But, between eukaryote and prokaryote HGT, there are still unexpressed statements that need to be explained before came up with a clear answer. A eukaryote without mitochondria and consisting of a prokaryotic system is still an interesting subject for mitochondrial evolution and related subjects. In the end, it seems like the evolution of mitochondria is still ongoing.
- Karnkowska A, Hampl V. The curious case of vanishing mitochondria. Microb Cell. Published online 2016. doi:10.15698/mic2016.10.531
- Karnkowska A, Vacek V, Zubáčová Z, et al. A eukaryote without a mitochondrial organelle. Curr Biol. Published online 2016. doi:10.1016/j.cub.2016.03.053
- Paul VD, Lill R. SnapShot: Eukaryotic Fe-s protein biogenesis. Cell Metab. Published online 2014. doi:10.1016/j.cmet.2014.07.010
- Burki F. Mitochondrial evolution: Going, going, gone. Curr Biol. Published online 2016. doi:10.1016/j.cub.2016.04.032
- Vacek V, Novak LVF, Treitli SC, et al. Fe-S cluster assembly in oxymonads and related protists. Mol Biol Evol. Published online 2018. doi:10.1093/molbev/msy168
- Paul VD, Lill R. Biogenesis of cytosolic and nuclear iron-sulfur proteins and their role in genome stability. Biochim Biophys Acta – Mol Cell Res. Published online 2015. doi:10.1016/j.bbamcr.2014.12.018
- Keeling PJ, Palmer JD. Horizontal gene transfer in eukaryotic evolution. Nat Rev Genet. Published online 2008. doi:10.1038/nrg2386
a) Paul VD, Lill R. SnapShot: Eukaryotic Fe-s protein biogenesis. Cell Metab. Published online 2014. doi:10.1016/j.cmet.2014.07.010
b) Karnkowska A, Vacek V, Zubáčová Z, et al. A eukaryote without a mitochondrial organelle. Curr Biol. Published online 2016. doi:10.1016/j.cub.2016.03.053
c) Keeling PJ, Palmer JD. Horizontal gene transfer in eukaryotic evolution. Nat Rev Genet. Published online 2008. doi:10.1038/nrg2386