Genome-wide RNAi Screen Identifies Romo1 as a Novel Regulator of Mitochondrial Fusion and Cristae Integrity

FieldValue
dc.contributor.authorNorton, Matthew
dc.date.accessioned2013-01-22T21:26:20Z
dc.date.available2013-07-22T10:00:04Z
dc.date.created2013
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/10393/23701
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-6672
dc.description.abstractMitochondria exist in a dynamic network regulated by the opposing processes of mitochondrial fusion and fission. Regulation of mitochondrial morphology is critical for metabolism, quality control and cell survival, among other cellular processes. Large GTPases are responsible for shaping the mitochondrial network. Mitofusins 1 and 2 and Opa1 regulate outer and inner mitochondrial membrane fusion, respectively. Conversely, Drp1 is recruited to mitochondria to carry out fission. Although many proteins have been implicated in these processes, there are still many unknowns. We sought to identify novel regulators of mitochondrial morphology and conducted a genome-wide RNAi screen to identify candidate genes. We identified Reactive Oxygen species Modulator 1 (ROMO1) as a novel regulator of mitochondrial fusion and cristae integrity. In the absence of ROMO1, the mitochondrial network fragments and cristae are lost. These defects lead to impaired mitochondrial respiration and sensitization to cytochrome c release and downstream apoptosis. ROMO1 is regulated by mitochondrial REDOX at 4 cysteine residues that couple REDOX signaling to mitochondrial morphology. We have characterized ROMO1 as an interactor with the MINOS complex, required for cristae junction maintenance, and the inner mitochondrial membrane fusion GTPase OPA1. Through these interactions ROMO1 couples cristae junction security to mitochondrial fusion.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectMitochondria
dc.subjectMitochondrial Dynamics
dc.subjectMitochondrial Fusion
dc.subjectROMO1
dc.subjectOPA1
dc.subjectROS
dc.subjectREDOX
dc.subjectCristae
dc.subjectApoptosis
dc.titleGenome-wide RNAi Screen Identifies Romo1 as a Novel Regulator of Mitochondrial Fusion and Cristae Integrity
dc.typeThesis
dc.faculty.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
dc.contributor.supervisorScreaton, Robert
dc.embargo.terms6 months
dc.degree.nameMSc
dc.degree.levelmasters
dc.degree.disciplineMédecine / Medicine
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
CollectionThèses, 2011 - // Theses, 2011 -

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