Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.726728
Title: Oxidative regulation mechanisms in the mitochondrial intermembrane space
Author: Manganas, Phanee
ISNI:       0000 0004 6421 856X
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2017
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Abstract:
Oxidative stress occurs when cells are unable to cope with the levels of various reactive oxygen species (ROS) that arise as part of regular cellular metabolism or in response to ionising radiation (H2O2, O2-, OH-). The most well studied ROS is H2O2, due to its dual role as a mediator of oxidative stress and a signalling molecule for many cellular pathways. Cells possess a number of different mechanisms to combat ROS, in order to prevent their levels from becoming toxic. In this thesis, we studied three different aspects of the antioxidant defence in Saccharomyces cerevisiae. In the first part, we explored the role of erythroascorbic acid – the yeast analogue of ascorbic acid (vitamin C) – and attempted to determine its role as an antioxidant in yeast. Our results were inconclusive, though there were indications that the presence of erythroascorbic acid may have a protective effect on the mitochondrial inner membrane potential (ΔΨ), protecting it from depolarisation. The second part focused on elucidating the mitochondrial targeting of the main H2O2 sensor Gpx3 and, more specifically, whether the Yap1-binding proteins, Ybp1 and Ybp2, have an effect on the import of Gpx3 in yeast mitochondria. Our results show a slight effect of Ybp1 (but not Ybp2) on the import of Gpx3, indicating that Ybp1 may act as a chaperone for the more efficient targeting of Gpx3 from the cytosol to the outer mitochondrial membrane and, as a result, its eventual translocation into the IMS. The final part of this thesis focused on elucidating the import of Trx1 and Trr1 in the mitochondrial IMS, as well as their function in this particular subcompartment. The discovery of two members of the thioredoxin system in the IMS is important, due to the absence of a known reducing mechanism in this oxidising compartment. Our results determined that several well-known import factors are dispensable for the import of either Trx1 or Trr1, indicating that they follow a yet unknown pathway for their translocation into the IMS. Importantly, we showed that Trx1 is reduced (and thus, active) in the IMS and that it can interact in vitro with both components of the MIA machinery (Mia40 and Erv1), while in organello experiments showed that Trx1 most probably interacts with a large number of Mia40 substrates.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.726728  DOI: Not available
Keywords: Q Science (General) ; QH301 Biology ; QH345 Biochemistry
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