Characterise novel functions of a V-ATPase complex component in lysosomal lipase delivery

Aging is associated with a decline in the ability of cells to degrade unwanted material. The build-up of undegraded material in cells can result in their dysfunction and is therefore associated with various aging-related diseases, including neurodegeneration and cancer. One of the major cellular hubs that mediate degradation processes is known as the lysosome. Lysosomes are specialised compartments that can degrade a wide range of substrates through the activities of specific enzymes. This localised activity of enzymes in lysosomes is essential to regulate their function. Therefore, cells have developed various mechanisms to deliver enzymes to lysosomes and ensure their restrained activity.

In this proposal, we aim to understand how lipids are degraded in lysosomes. The degradation of lipids is mediated by a subset of enzymes known as lipases. We have identified a novel mechanism in cells that delivers lipases to lysosomes. We aim to understand the molecular bases of this mechanism and what happens in cells when it is disrupted. We will address whether enhancing this lipase delivery pathway can prolong longevity in order to confirm its relevance during aging.

This proposal aims to understand mechanisms underlying aging and we predict that our findings may help us improve healthy aging in humans. Our goal is to uncover the molecular details of how our cells function and remain healthy in order to help us design methods to improve healthy aging and delay the onset of disorders in humans. The findings and tools generated during the course of this study will also have wider implications and utilities across multiple research areas.