Mitochondria are essential organelles that perform many critical metabolic functions but are also a major source of damaging reactive oxygen species (ROS) and harbour pro-apoptotic factors. Multiple homeostatic processes operate to maintain mitochondrial integrity; however, terminally damaged organelles are degraded through the process of targeted mitochondrial autophagy (mitophagy) to prevent potentially catastrophic consequences. Such homeostatic mechanisms are particularly important for post-mitotic, energetically demanding tissues such as nerves and muscles. There is increasing evidence that failure of this mechanism is linked to normal ageing and some neurodegenerative disorders. Interestingly, two proteins linked to Parkinson’s Disease (PD), Parkin, a cytosolic ubiquitin ligase, and PINK1, a mitochondrially targeted kinase, have been shown to play key roles in this mitophagy. However, little is known about their impact on basal mitophagy in vivo. Moreover, while the consequences of mitophagy defects and the mechanisms that lead to neuronal cell death are currently unclear, aberrant induction of inflammatory signalling is becoming recognised as a key pathogenic mechanism in PD. The work conducted for this thesis aimed to explore the activation of the innate immune system, in the context of PD, using in Drosophila as an in vivo model. First, to analyse mitophagy events in vivo, I developed and characterised transgenic Drosophila expressing the fluorescent mitophagy reporters, the mt-Keima and the mito-QC, were generated to evaluate the impact of Pink1/parkin mutations on basal mitophagy under physiological conditions. My results show that mitophagy is readily detectable and abundant in many tissues including the PD-relevant dopaminergic neurons. However, mitolysosomes were almost completely absent in flight muscles. mechanism associated with the PINK1/Parkin pathway. My work provides evidence that Pink1 and parkin are not essential for bulk basal mitophagy in Drosophila. They also emphasize that mechanisms underpinning basal mitophagy remain largely obscure. Recently, aberrant activation of immune signalling triggered by the DNA-sensing receptor cyclic GMP–AMP synthase (cGAS) and its downstream signalling effector stimulator of interferon genes (STING) has been implicated in PINK1/Parkin pathology. In order to determine whether the role of Sting in the Pink1/parkin pathology is conserved in Drosophila, I analysed loss of Sting coupled with Pink1/parkin mutants. My work demonstrates that loss of Sting, or the downstream effector Relish, is not sufficient to rescue the behavioural defects or the disruption of the mitochondrial integrity of Pink1/parkin mutant flight muscles, indicating that these phenotypes are not due to aberrant activation of the cGAS-STING pathway in Drosophila. In a broader effort to understand the involvement of the immune system in the Pink1/parkin pathology, I knocked down key components involved in various other immune pathways, in combination with Pink1 and parkin mutants. Like the Sting axis, most of the immune pathways investigated did not seem to modify Pink1 and parkin mutant phenotypes; however, my data revealed that knockdown of key players of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway significantly improved Pink1 mutant phenotypes. Interestingly, this genetic interaction seems to be restricted to Pink1 as loss of JAK/STAT components failed to modify the parkin mutant phenotypes. Although further work needs to be carried out to in order to understand the mechanism behind the interaction between Pink1 and the JAK/STAT pathway, these findings suggest that dowregulation of the particular pathway could be considered as a new therapeutic intervention for PD.