dictyNews

Electronic Edition

Volume 44, number 32

November 16, 2018



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Abstracts

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Exploring the Effect of Rotenone—A Known Inducer of Parkinson’s 

Disease—On Mitochondrial Dynamics in Dictyostelium discoideum



Ethan Chernivec, Jacie Cooper and Kari Naylor*



Department of Biology, University of Central Arkansas, Conway, 

AR 72035, USA;

* Correspondence: [log in to unmask]; Tel.: +1-501-450-5826





Cells, accepted   https://www.mdpi.com/2073-4409/7/11/201



Current treatments for Parkinson’s disease (PD) only alleviate 

symptoms doing little to inhibit the onset and progression of the 

disease, thus we must research the mechanism of Parkinson’s. 

Rotenone is a known inducer of parkinsonian conditions in rats; 

we use rotenone to induce parkinsonian cellular conditions in 

Dictyostelium discoideum. In our model we primarily focus on 

mitochondrial dynamics. We found that rotenone disrupts the 

actin and microtubule cytoskeleton but mitochondrial morphology 

remains intact. Rotenone stimulates mitochondrial velocity while 

inhibiting mitochondrial fusion, increases reactive oxygen species 

(ROS) but has no effect on ATP levels. Antioxidants have been 

shown to decrease some PD symptoms thus we added ascorbic 

acid to our rotenone treated cells. Ascorbic acid administration 

suggests that rotenone effects may be specific to the disruption of 

the cytoskeleton rather than the increase in ROS. Our results imply 

that D. discoideum may be a valid cellular PD model and that the 

rotenone induced velocity increase and loss of fusion could prevent 

mitochondria from effectively providing energy and other 

mitochondrial products in high demand areas. The combination of 

these defects in mitochondrial dynamics and increased ROS 

could result in degeneration of neurons in PD.





submitted by:  Kari Naylor [[log in to unmask]]

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Gamma-secretase orthologues are required for lysosomal activity and 

autophagic degradation in Dictyostelium discoideum, independent of 

Presenillin proteolytic function



Devdutt Sharma, Grant Otto, Eleanor C. Warren, Philip Beesley, 

Jason S. King and Robin S.B. Williams 





Autophagy, in press



Mutations in the gamma-secretase complex are strongly associated 

with familial Alzheimers disease. Both proteolytic and non-proteolytic 

functions for the gamma-secretase complex have been previously 

described in mammalian model organisms, but their relative 

contributions to disease pathology remain unclear. Here, we dissect 

the roles of orthologues of the gamma-secretase components in the 

model system Dictyostelium, focusing on endocytosis, lysosomal 

activity and autophagy. In this model, we show that the orthologues 

of presenilin, nicastrin/Ncstn and anterior pharynx defective 1/Aph-1, 

are necessary for optimal fluid-phase uptake by macropinocytosis and 

in multicellular development under basic condition. Disruption of either 

presenilin or Aph-1 proteins also leads disrupted phagosomal 

proteolysis as well as decreased autophagosomal acidification and 

autophagic flux. This indicates a general defect in lysosomal trafficking 

and degradation, which we show leads to the accumulation of 

ubiquitinated protein aggregates in cells lacking presenillin and Aph-1 

proteins. Importantly, we find that all the endocytic defects observed in 

Dictyostelium presenilin mutants can be fully rescued by proteolytically 

inactive Dictyostelium presenilin and human presenilin 1 proteins. Our 

data therefore demonstrates an evolutionarily conserved non-

proteolytic role for presenilin, and gamma-secretase orthologues, in 

maintaining Dictyostelium lysosomal trafficking and autophagy.





submitted by:  Robin Williams [[log in to unmask]]

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[End dictyNews, volume 44, number 32]