Frataxin & evolution of multicellularity

Loss of frataxin is lethal in multicellular organisms. Why is frataxin necessary for multicellular life?

Use of Game-Theoretical Methods in Biochemistry and Biophysics [2008] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577752/

"Recently, it has been shown experimentally that stimulation of respiration by frataxin in colon cancer cells reduced growth rate [47]. Thus, cancer can be regarded as a regression to selfish behaviour of cells. Healthy higher organisms possess regulation mechanisms to suppress cancer. However, in early evolution of multicellularity, these mechanisms probably did not yet exist."

So that's one reason.

Could there be some relationship to osmoregulation?

2020-6-10

Osmoregulation implies maintenance of electrochemical gradients, just as multicellularity implies morphogenesis. Then I remembered Dr Michael Levin's talk on bioelectric fields and morphogenesis:

Of course, since comments are turned off I can't make my notes in the YT comments and use the nifty little timestamp feature. Will have to come back to it and make notes as well as locate some of the slides, some of which feature Na/K ATPase [22:14].

Went on to watch an interview with Dr Michael Levin (also no comments allowed):

[2020-11-08]

Watched a wonderful three-part lecture series on the cytoskeleton and cell motility by Dr Julie Theriot (2016) a few days ago. In the last video in the series, she discussed the evolution of eukaryotes and put forth the hypothesis that eukaryotic life requires nucleators and molecular motor proteins:

 

Of course, I searched on actin and frataxin and found the following, published in March:

 

Muñoz-Lasso, Diana C., Belén Mollá, Pablo Calap-Quintana, José Luis García-Giménez, Federico V. Pallardo, Francesc Palau, and Pilar Gonzalez-Cabo. “Cofilin Dysregulation Alters Actin Turnover in Frataxin-Deficient Neurons.” Scientific Reports 10, no. 1 (March 23, 2020): 5207. https://doi.org/10.1038/s41598-020-62050-7.

 

        What is the relationship between multicellularity and  electrochemical gradients / bioelectric fields? Looks like it has to do with the cytoskeleton:

 

Weiß, Isabel, and Johannes Bohrmann. “Electrochemical Gradients Are Involved in Regulating Cytoskeletal Patterns during Epithelial Morphogenesis in the Drosophila Ovary.” BMC Developmental Biology 19, no. 1 (12 2019): 22. https://doi.org/10.1186/s12861-019-0203-y.

"... gradual modifications of electrochemical signals can serve as physiological means to regulate cell and tissue architecture by modifying cytoskeletal patterns."

"Correlations between stage-specific bioelectrical properties and cytoskeletal patterns observed in the FCE of Drosophila were confirmed by the application of inhibitors of several ion-transport mechanisms. We conclude that the changes of pH_i- [intracellular pH] and V_mem-gradients induced by inhibitors simulate electrochemical changes that occur naturally, resulting in the cytoskeletal changes observed during differentiation of the FCE. Our results support the hypothesis that electrochemical signals play important roles in the regulation of cell and tissue architecture by organising elements of the MF- and MT-cytoskeleton. It remains to be shown which specific elements are affected by these signals."

Recently I have been reading up on the epithelial sodium channel (ENac), which is not exclusively expressed in epithelial cells but also in other cell types such as vascular endothelial cells. Reciprocal interactions between the cytoskeleton and ion channels and also aquaporins is an active topic of research.

2021-01-21

Frataxin also decreases propensity to ferroptosis since it reduces free intracellular iron - so it looks like it could either promote or inhibit cancer, depending on the circumstances.

Identification of frataxin as a regulator of ferroptosis [2020]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068686/pdf/main.pdf