Mitochondria are energy-producing organelles. They are highly adaptive and undergo the processes of fusion and fission to couple mitochondrial function with changing cellular demands. In this thesis, I have identified a new molecular mechanism involving TAp73/OPA1 that controls mitochondrial morphology (Buckley et al., 2020). OPA1 drives fusion of the inner mitochondrial membrane and controls cristae remodelling, a process facilitating the execution of apoptosis. I have shown that TAp73 regulates OPA1 expression in TAp73-/- cell lines which were generated using CRISPR/Cas9 targeting. Concurrently, I show that disruption of this TAp73/OPA1 axis results in a fragmented mitochondrial network owing to impaired mitochondrial fusion. Disruption of this axis also reduces the capacity for TAp73-/- cells to produce energy via oxidative phosphorylation. Further, the ectopic expression of OPA1 in TAp73-/- cells rescued defective mitochondria and restored bioenergetic function, placing OPA1 downstream of TAp73 in the regulation of mitochondrial dynamics. Decreased expression of OPA1 also results in altered cristae structure in cellular and in vivo models with deletion of TAp73. Importantly, owing to the role of OPA1 in modulating cytochrome c release, TAp73-/- cells have an increased sensitivity to apoptotic cell death, e.g., on exposure to BH3-mimetics. Further, many cancers such as lung and colon have upregulated expression of TAp73 which is associated with poor survival outcomes. This raises the possibility that the TAp73/OPA1 axis may be hijacked in cancer to evade apoptotic cell death and increase energy production, thereby facilitating tumorigenesis and supporting a growth-promoting role of TAp73 isoforms. This TAp73/OPA1 axis is also important in the respiratory system, owing to high levels of TAp73 expression in airway epithelial cells. Indeed, the correct ciliation of airway cells is severely perturbed in TAp73 null mice. I therefore propose that these profound defects in ciliogenesis may be driven by dysregulated mitochondrial function. This was highlighted by the fact that the airway epithelium of p73 null mice displayed downregulation of OPA1 and an altered morphology of the mitochondrial network in the ciliated cell lineage. Further, defective cilia have a reduced capacity for mucociliary clearance of inhaled toxic particles. Loss of TAp73 function and the concomitant increase in sensitivity to apoptosis may therefore further enhance vulnerability to inhaled pathogens or pollutants, highlighting a possible role for TAp73 in the incidence and progression of airway diseases such as COPD.