Specific Protein Isoforms of Miro and Milton Have Divergent Roles Controlling Mitochondrial Transport, Fusion & Fission, and Health

Persistent Link:
http://hdl.handle.net/10150/244404
Title:
Specific Protein Isoforms of Miro and Milton Have Divergent Roles Controlling Mitochondrial Transport, Fusion & Fission, and Health
Author:
Langston, Rachel Elizabeth
Issue Date:
May-2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Neurons depend on mitochondria to produce ATP, regulate calcium signaling/homeostasis, and control apoptosis. Motor proteins of the kinesin and dynein families actively transport mitochondria through axons. Miro and Milton are two proteins responsible for linking kinesin to mitochondria, and Miro regulates dynein-based transport. Drosophila Miro (dMiro) has three isoforms (dMiro-M, -L, and -S). Milton has four: Milton-A, -B, -C, and -D. To study the role of the dMiro isoforms, we expressed a transgene of each in a dmiro null background, and examined their phenotypic effects on mitochondrial distribution, transport, and morphology in motor neuron axons by using live time-lapse imaging of GFP-tagged mitochondria. The potential role of the Milton-A isoform was examined by chronically or acutely overexpressing (OE) the transgene in motor neurons. We found that Milton-A OE causes a massive loss of mitochondria within 20 hours. In dMiro-L and -S rescues, compared to wildtype, there was decrease the total mitochondrial density, but not the percent of motile mitochondria. To determine components of the signaling pathway controlled by Miro-L and -S, we performed a genetic screen to isolate dominant suppressor mutations of the lethal overexpression phenotypes of dMiro-L and -S. Many suppressor mutations were isolated and mapped to specific chromosomes.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Molecular and Cellular Biology
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleSpecific Protein Isoforms of Miro and Milton Have Divergent Roles Controlling Mitochondrial Transport, Fusion & Fission, and Healthen_US
dc.creatorLangston, Rachel Elizabethen_US
dc.contributor.authorLangston, Rachel Elizabethen_US
dc.date.issued2012-05-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractNeurons depend on mitochondria to produce ATP, regulate calcium signaling/homeostasis, and control apoptosis. Motor proteins of the kinesin and dynein families actively transport mitochondria through axons. Miro and Milton are two proteins responsible for linking kinesin to mitochondria, and Miro regulates dynein-based transport. Drosophila Miro (dMiro) has three isoforms (dMiro-M, -L, and -S). Milton has four: Milton-A, -B, -C, and -D. To study the role of the dMiro isoforms, we expressed a transgene of each in a dmiro null background, and examined their phenotypic effects on mitochondrial distribution, transport, and morphology in motor neuron axons by using live time-lapse imaging of GFP-tagged mitochondria. The potential role of the Milton-A isoform was examined by chronically or acutely overexpressing (OE) the transgene in motor neurons. We found that Milton-A OE causes a massive loss of mitochondria within 20 hours. In dMiro-L and -S rescues, compared to wildtype, there was decrease the total mitochondrial density, but not the percent of motile mitochondria. To determine components of the signaling pathway controlled by Miro-L and -S, we performed a genetic screen to isolate dominant suppressor mutations of the lethal overexpression phenotypes of dMiro-L and -S. Many suppressor mutations were isolated and mapped to specific chromosomes.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineMolecular and Cellular Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
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