Does primary very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency cause secondary defects in mitochondrial oxidative phosphorylation?

Clark, Hayley 2019, Does primary very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency cause secondary defects in mitochondrial oxidative phosphorylation?, B.Science (Hons thesis, School of Life and Environmental Sciences, Deakin University.

Attached Files
Name Description MIMEType Size Downloads

Title Does primary very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency cause secondary defects in mitochondrial oxidative phosphorylation?
Author Clark, Hayley
Institution Deakin University
School School of Life and Environmental Sciences
Faculty Faculty of Science, Engineering and Built Environment
Degree type Honours
Degree name B.Science (Hons
Thesis advisor McKenzie, MatthewORCID iD for McKenzie, Matthew orcid.org/0000-0001-7508-1800
Date submitted 2019-11-08
Keyword(s) mitochondria
acly-coA dehydrogenase
fatty acid oxidation
Summary Very long-chain acyl-coA dehydrogenase (VLCAD) is responsible for catalysing the first step in the fatty acid β-oxidation (FAO) pathway. Deficiencies associated with VLCAD result in an energy deficit, as the FAO and oxidative phosphorylation (OXPHOS) pathways of the mitochondria are critical for energy production. VLCAD deficiency is associated with a variable phenotype, often involving cardiomyopathy, heart arrythmias, hepatic failure and sudden unexplained death. While VLCAD deficiency primarily disrupts FAO, secondary defects in oxidative phosphorylation (OXPHOS) may also contribute to disease pathogenesis, with physical interactions between VLCAD and OXPHOS proteins postulated in previous research. Therefore, secondary biochemical and physical defects of the OXPHOS pathway were investigated in VLCAD deficient fibroblasts to determine if they contribute to disease pathogenesis. Aspects of disease pathophysiology examined included OXPHOS complex assembly and stability, mitochondrial reactive oxygen species (ROS) production and cellular respiration.
VLCAD deficiency was not found to affect OXPHOS complex assembly or stability. Increased cellular ROS production was detected in VLCAD deficient cells compared to controls, with ROS generation in VLCAD deficient cells also associated with increased sensitivity to OXPHOS inhibition. VLCAD deficiency was not found to impair basal mitochondrial respiration, in fact, an increase was observed in a potential compensatory mechanism. Overall, the findings suggest that VLCAD deficient cells may have an enhanced anti-oxidant response to compensate for increased ROS production, potentially from complex III. These findings may indicate a novel disease-specific mechanism which, following further investigation, would strengthen our understanding of VLCAD deficiency pathogenesis in hope of expanding treatment options.
Language eng
Indigenous content off
Field of Research 0601 Biochemistry and Cell Biology
Description of original 63 p.
Copyright notice ©All rights reserved
Persistent URL http://hdl.handle.net/10536/DRO/DU:30133307

Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 0 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 28 Abstract Views, 0 File Downloads  -  Detailed Statistics
Created: Thu, 02 Jan 2020, 09:10:04 EST by Bernadette Admin Houghton

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.