Mitochondrial haemoglobin and ATP synthase – molecular interactions in health and disease

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Ebanks, Brad (2023) Mitochondrial haemoglobin and ATP synthase – molecular interactions in health and disease. PhD thesis, University of Nottingham.

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Abstract

The mitochondrial ATP synthase is a fundamental enzyme to multicellular life, as it is responsible for producing the vast majority of cellular adenosine triphosphate (ATP). Its molecular structure and enzymatic function have been widely studied to date. Here I have investigated the broader range of interactions that the enzyme participates in, including with mitochondrial haemoglobin, across a range of different species and under hypoxic conditions. I have also sought to understand potential changes in the activity and expression of mitochondrial ATP synthase in the skeletal muscle mitochondria of humans with chronic obstructive pulmonary disease (COPD) in response to exercise, as well as broader changes to the mitochondrial proteome.

Within this thesis I present data that demonstrate that the interactome of mitochondrial ATP synthase is associated with the translational silencing of the iron oxidase enzyme ceruloplasmin. I also present evidence of a molecular interaction with mitochondrial haemoglobin, and that this interaction may be part of a broader hypoxic response within the mitochondria. I show that the expression and activity of ATP synthase does not change in response to the studied exercise conditions in COPD, but that the expression of proteins associated with mitochondrial structure and morphology do change.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Chakrabarti, Lisa
Scott, David
Keywords: Cellular adenosine triphosphate; Mitochondrial haemoglobin; Hypoxic conditions; Skeletal muscle mitochondria; Chronic obstructive pulmonary disease; Mitochondrial proteome
Subjects: R Medicine > RB Pathology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Item ID: 73479
Depositing User: Ebanks, Brad
Date Deposited: 31 Jul 2023 04:41
Last Modified: 31 Jul 2023 04:41
URI: https://eprints.nottingham.ac.uk/id/eprint/73479

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