Use this URL to cite or link to this record in EThOS:
Title: The function of respiratory complex I in plants and in human disease
Author: Maclean, Andrew
ISNI:       0000 0004 7231 8501
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Access from Institution:
Complex I is the largest complex in the mitochondrial respiratory chain. Defects in complex I are a major cause of mitochondrial disease in humans. Mutations in the assembly factor NUBPL have been implicated in causing complex I deficiency. To assign pathogenicity to patient NUBPL variants, I used a yeast model, Yarrowia lipolytica, and recreated the corresponding amino acid changes in the Ind1 homolog. Using a combination of BN-PAGE, Western blotting and enzymatic analysis I was able to assign pathogenicity to four of the six variants as well as furthering our understanding of the role of Ind1 in complex I assembly. Complex I has been lost in the course of evolution in several unicellular eukaryotes, but never in multicellular eukaryotes. Recently, two studies found that the mitochondrial genes encoding complex I subunits were lacking in the genus Viscum. To investigate if complex I has been lost, I isolated mitochondria from European Mistletoe, Viscum album. My results from BN-PAGE and proteomic analysis indicate that complex I has been lost. Complex I requires FeS clusters, which are delivered by the mitochondrial ISC pathway. To better understand this process in plants, I characterised the role of FeS carrier proteins NFU4, NFU5 and GRXS15 in Arabidopsis thaliana. NFU4 and NFU5 were found to be genetically redundant but when combined as a double mutant were embryo lethal. This suggest that NFU4 and NFU5 play an important role in FeS assembly. Mutants in GRXS15 had a severe growth phenotype, but normal levels of respiratory complexes, suggesting GRXS15 plays a secondary role in FeS cluster assembly. Understanding complex I will be important in the future for helping to treat human mitochondrial disorders. In addition, studying complex I in plants, including in non-model organisms, helps further our understanding of its function and evolution.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available