Browsing by Author "Chakrabarti, Lisa"
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Item Open Access The dysregulated Pink1- Drosophila mitochondrial proteome is partially corrected with exercise(2021-01-06) Moisoi, Nicoleta; Ebanks, B.; Ingram, T. L.; Katyal, G.; Ingram, J. R.; Chakrabarti, LisaOne of the genes which has been linked to the onset of juvenile/early onset Parkinson’s disease (PD) is PINK1. There is evidence that supports the therapeutic potential of exercise in the alleviation of PD symptoms. It is possible that exercise may enhance synaptic plasticity, protect against neuro-inflammation and modulate L-Dopa regulated signalling pathways. We explored the effects of exercise on Pink1 deficient Drosophila melanogaster which undergo neurodegeneration and muscle degeneration. We used a ‘power-tower’ type exercise platform to deliver exercise activity to Pink1- and age matched wild-type flies. Mitochondrial proteomic profiles responding to exercise were obtained. Of the 516 proteins identified, 105 proteins had different levels between Pink1- and wild-type (WT) non-exercised D. melanogaster. Gene ontology enrichment analysis and STRING network analysis highlighted proteins and pathways with altered expression within the mitochondrial proteome. Comparison of the Pink1-exercised proteome to WT proteomes showed that exercising the Pink1- flies caused their proteomic profile to return towards wild-type levels.Item Open Access Exercising D. melanogaster modulates the mitochondrial proteome and physiology - the effect on lifespan depends upon age and sex(2021-10-27) Ewbanks, B.; Wang, Y.; Katyal, G.; Sargent, C.; Ingram, T.L.; Bowman, A.; Moisoi, Nicoleta; Chakrabarti, LisaAgeing is a major risk factor for many of the most prevalent diseases, including neurodegenerative disease, cancer and heart disease. As the global population continues to age, behavioural interventions that can promote healthy ageing will improve quality of life and relieve the socio-economic burden that comes with an aged society. Exercise is recognised as an effective intervention against many diseases of ageing, but we don’t know the stage in an individual’s lifetime in which exercise is most effective at promoting healthy ageing and whether it has a direct effect on lifespan. We exercised w 118 Drosophila melanogaster, interrogating effects of sex and group size, at different stages of their lifetime and recorded their lifespan. Climbing scores at 30 days were measured to record differences in fitness in response to exercise. We also assessed the mitochondrial proteome of w1118 Drosophila that had been exercised for one week, alongside mitochondrial respiration measured using High-Resolution Respirometry, to determine changes in mitochondrial physiology in response to exercise. We found that age-targeted exercise interventions improve lifespan in male and female Drosophila, and grouped males exercised in late life had improved climbing scores, when compared with those exercised throughout their entire lifespan. The proteins of the electron transport chain were significantly upregulated in expression after one week of exercise, and complex II linked respiration was significantly increased in exercised Drosophila. Taken together our study provides a basis to test specific proteins and complex II of the respiratory chain as important effectors of exercise induced healthy ageing.Item Open Access Mitochondrial Haemoglobin Is Upregulated with Hypoxia in Skeletal Muscle and Has a Conserved Interaction with ATP Synthase and Inhibitory Factor 1(MDPI, 2023-03-16) Moisoi, Nicoleta; Ebanks, Brad; Katyal, Gunjan; Taylor, Chris; Dowie, Adam; Papetti, Chiara; Lucassen, Magnus; Chakrabarti, LisaThe globin protein superfamily has diverse functions. Haemoglobin has been found in non-erythroid locations, including within the mitochondria. Using co-immunoprecipitation and in silico methods, we investigated the interaction of mitochondrial haemoglobin with ATP synthase and its associated proteins, including inhibitory factor 1 (IF1). We measured the expression of mitochondrial haemoglobin in response to hypoxia. In vitro and in silico evidence of interactions between mitochondrial haemoglobin and ATP synthase were found, and we report upregulated mitochondrial haemoglobin expression in response to hypoxia within skeletal muscle tissue. Our observations indicate that mitochondrial pH and ATP synthase activity are implicated in the mitochondrial haemoglobin response to hypoxia.Item Open Access Mitochondrial homeostasis in cellular models of Parkinson's disease(Mitofit, 2021-10-06) Moisoi, Nicoleta; Jakovljevic, N. K.; Ebanks, B.; Chakrabarti, Lisa; Markovic, I.Mitochondrial function is known to be an important factor in maintaining cellular homeostasis and its dysregulation has become a hallmark for multiple disease conditions. This review aims to sythesise the extent of this knowledge by analysing changes of mitochondrial physiology parameters in Parkinson’s disease (PD) and to evaluate the contribution of cellular models of PD in the field. The analysis provided here constitutes a platform for further elucidation of mitochondrial function parameters relative to factors that may potentiate disease progression.