Abstract: Mitochondria are well known for their function in energy production; however they also play a crucial role in phospholipid transfer, inflammation, calcium balance and cell death, positioning them as a central regulator of cellular homeostasis. The cell therefore relies on quality control mechanisms to limit mitochondrial damage and the production of harmful reactive oxygen species (ROS). To date, numerous mitochondrial quality control (mitoQC) pathways have been defined, with mitophagy, the autophagic degradation of entire mitochondria, being the most extensively studied. Locally directed repair pathways also exist and we have recently elucidated key mechanisms of one of these mitochondrial stress response pathways regulated by the endosomal adaptor – Toll-interacting protein (Tollip) (Ryan et al., 2020). In this pathway, damaged mitochondrial proteins and lipids are selectively transported as mitochondrial-derived vesicles (MDVs) into the endolysosomal system to facilitate cargo degradation. However, these MDVs are heterogeneous, with each discrete cargo trafficked via a specific route and destination. Since their initial identification demonstrating the segregation of the outer membrane mitochondrial-anchored protein ligase and its subsequent shuttling to peroxisomes (Neuspiel et al., 2008), MDVs have been shown to incorporate a host of different proteins from the inner and outer membranes or matrix. Indeed, it appears their cargo and potentially their membrane composition defines the trafficking machinery required, the particular route taken and their destination.