EFFECT OF DMIRO OF MITOCHONDRIAL TRANSPORT AND MORPHOLOGY

picture of Terra Kuhn presenting his/her poster: EFFECT OF DMIRO OF MITOCHONDRIAL TRANSPORT AND MORPHOLOGY

Terra Kuhn , Milos Babic, Konrad Zinsmaier

EFFECT OF DMIRO OF MITOCHONDRIAL TRANSPORT AND MORPHOLOGY

In neuronal cells, high levels of energy are required to allow signal transduction between cells. To provide this energy, mitochondria, the power-producing organelles of the cell, must be transported into axons and dendrites, all the way to the synapse. This distance can be thousands or millions of times greater than the length of the cell body. Previous work by our lab and others have shown the importance of the mitochondrial protein Miro in regulation of this transport. Without Miro present, mitochondrial transport in axons is almost completely abolished, and the result in Drosophila larvae is lethality after the 3rd instar stage.

Alternative splicing of the so-called “variable domain” of the Miro protein leads to three isoforms, labeled Long, Medium, and Short (based on their total amino acid length). In wild type flies, all three copies are expressed, but the reason for their existence remains unknown, as does any difference in their function. To further explore this question, additional copies of each splice form have been expressed in Drosophila melanogaster larvae, both in wildtype and in Miro null backgrounds. Using confocal microscopy, we assessed the structural and functional effects of this genetic manipulation on mitochondria in larval motor neurons.

Our results show that expression of all Miro isoforms in wild type background reduces motile mitochondrial density, while the long and middle splice form also reduced overall mitochondrial density. All three forms reduced both retrograde and anterograde mitochondrial flux. Additionally, the long and short splice forms caused elongation of anterogradely-moving mitochondria, while the long splice form also elongated retrogradely moving organelles.

When expressed in Miro null background, all three splice forms reduce total mitochondrial density, but only long and short isoforms reduce density of motile mitochondria. All splice forms were found to have lower retrograde flux, and long and short versions were found to have lower anterograde flux as well. The short splice form increased the length of anterogradely moving mitochondria, while the other two isoforms had no effect.

 

Research Funding Source: HHMI

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