MAPPING MITOCHONDRIA-ORGANELLE CONTACT SITES DURING NEURONAL AGEING AND NEURODEGENERATION

Mitochondria are social organelles that form contacts with most, if not all, organelles in a cell. Mitochondria-organelle contact sites (MOCS) are integral to cellular homeostasis and therefore cell survival. However, very little is known about the behaviour of MOCS in the context of ageing and disease, specifically in in vivo models. This project aims to advance the understanding of MOCS in the context of neurodegenerative diseases and ageing through the use of Drosophila melanogaster.
To characterise MOCS in vivo, we use transgenic Drosophila expressing split-GFP-based contact sites sensors (SPLICS). SPLICS are proximity-based sensors ideal for the characterisation of MOCS in live cells. Combined with confocal imaging, they are a powerful tool for observing contact site distribution in live organisms.
Using SPLICS to investigate mitochondria-lysosome (MT.LO) and mitochondria-peroxisome (MT.PO) contact sites, I will discuss the spatial distribution SPLICS signal in peripheral and central nervous system neurons of Drosophila. Furthermore, I will describe how age and disease-related proteins, specifically ALS-related dipeptide repeat proteins (DPRs), can alter the expression and distribution of the SPLICS probes in Drosophila​​​​.
Leveraging our recent work (PMID: 40148280, DOI: 10.1038/s41419-025-07511-5), I will discuss how my findings expand on the current knowledge of MOCS in models of neurodegenerative disease through the lens of MT.LO and MT.PO contact sites and highlight the need for research into cell-type specific MOCS organisation.