Mechanisms of Dnm1p-mediated mitochondrial fission.

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Title Mechanisms of Dnm1p-mediated mitochondrial fission.
Publication Type dissertation
School or College School of Medicine
Department Biochemistry
Author Karren, Mary Anne
Date 2007-05
Description Mitochondria are semiautonomous organelles essential for eukaryotic life. Mitochondria house the machinery required for cellular respiration and energy production, and hundreds of enzymes required for essential biochemical pathways. Mitochondrial number and distribution are regulated by coordinated mitochondrial fission, fusion, and movement events, and must continually adapt to meet the changing spatial and temporal energy requirements of growing cells. In recent years, it has become clear that defects in mitochondrial fission, fusion, or movement can lead to cellular dysfunction and disease. This dissertation investigates the molecular basis for the process of mitochondrial fission in the budding yeast, Saccharomyces cerevisiae . Mitochondrial fission is mediated by macromolecular protein complexes localized to the cytoplasmic face of the outer mitochondrial membrane. These complexes are composed of at least three components, Dnm1p, Fis1p, and Mdv1p. Studies presented in this dissertation investigate the coordinated series of inter- and intramolecular interactions required to recruit and assemble these three proteins into functional fission complexes. Studies detailed in Chapter 2 suggest that the cytoplasmic domain of Fis1p interacts directly with Mdv1p, and that this interaction is required for the recruitment of Dnm1p to functional fission complexes. Results presented in Chapter 3 demonstrate that dimeric Dnm1p is initially recruited to mitochondria, and that higher-ordered Dnm1p oligomerization occurs after mitochondrial recruitment. In addition, Chapter 3 suggests that GTP hydrolysis by Dnm1p is required to destabilize mitochondrial fission complexes after fission occurs. Analyses presented in Chapter 4 characterize the domain of Dnm1p required for Dnm1p association with the actin cytoskeleton. Together, these studies comprise a significant advance in our understanding of the molecular basis for mitochondrial fission, and raise important issues for future study.
Type Text
Publisher University of Utah
Subject Genetics; DNA, Mitochondrial
Subject MESH Mitochondria; Saccharomyces cerevisiae
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Mechanisms of Dnm1p-mediated mitochondrial fission." Spencer S. Eccles Health Sciences Library. Print version of "Mechanisms of Dnm1p-mediated mitochondrial fission." available at J. Willard Marriott Library Special Collection. QH9.7 2007 .K37.
Rights Management © Mary Anne Karren
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,23956
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available). "Original missing pg. ix. Scanned as received."
ARK ark:/87278/s6v70014
Setname ir_etd
ID 192086
Reference URL https://collections.lib.utah.edu/ark:/87278/s6v70014
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