Buso 2017 Thesis
| Buso A (2017) Mitochondrial oxidative phosphorylation plasticity/adaptation triggered by disturbances and stresses and targeted by therapies. PhD Thesis p110. |
ยป [dspace-uniud.cineca.it/handle/10990/805 Open Access]
Buso A (2017) PhD Thesis
Abstract: Mitochondrion is an important organelle for cells survival. In fact, it is responsible for many processes such as cellular metabolism, i.e. oxidative phosphorylation for ATP production, energy homeostasis and regulation of apoptosis and autophagy. Mitochondrion, due to this role, needs to be โplasticโ in order to respond and adapt quickly to any perturbation and change of conditions in the different tissues of the human body. The induction of mitochondria biogenesis is required to meet different energetic demands under stress conditions. Thus, mitochondrial plasticity is the mechanism that controls modification in conditions of cellular stress or in response to environmental stimuli like exercise, caloric restriction, cold exposure, oxidative stress, cell division and renewal, and differentiation. Recently, mitochondrial modulation has become also a topic of interest as a therapeutic target. The master regulator gene of mitochondrial biogenesis is PGC1ฮฑ that, through nuclear transcription factors and subsequent metabolic sensors and other signalling proteins, is capable to modulate mitochondrial abundance, activity and oxidative phosphorylation as a consequence of energy homeostasis unbalance. Mitochondrial plasticity during the last few years was extensively studied in skeletal muscle models, due to its fast adaptation in exercise and rest condition, but also in cancer cachexia, ageing and heart disease. Also in cancer, mitochondrial adaptations have become a fundamental topic, in particular to understand the underling pathogenic mechanism of disease progression, to identify prognostic factors and to design adjuvant therapies targeting mitochondria.
In this frame, this PhD Thesis investigates the role and adaptations of mitochondria in different pathophysiological models of skeletal muscle and brain tumors.
The expression of some key proteins of the signalling pathways involved in mitochondrial biogenesis regulation, such as PGC1ฮฑ, LKB1-AMPK an energy sensing axis, Sirt3 a regulator of mitochondrial enzymes functionality, are investigated together with the OXPHOS complexes, HSP60, CS and TOM20 as mitochondrial mass markers.
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