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Lysosome-mitochondria miscommunication in lysosomal storage disease
Join us in person or remotely via Teams - e-mail carolyn.thackrah@pharm.ox.ac.uk for joining instructions
Organelle membrane contact sites orchestrate inter-organelle communication that is essential for cellular homeostasis. However, aberrant crosstalk between lysosomes and mitochondria has been linked with neurodegenerative disease.
The lysosomal storage disease Niemann-Pick disease type C (NPC) is caused by loss of function mutations in the (LE/Lys) lipid transport proteins NPC1 or NPC2. The resulting accumulation of lysosomal lipids in NPC has complex downstream consequences including mitochondrial dysfunction, which is thought to be a key driver of disease pathogenesis. How a defect in a lysosomal lipid transport protein causes mitochondrial dysfunction is not fully understood, but we identified expanded mitochondria:lysosome contact sites (MLCs) in NPC1-deficient cells.
Membrane contact sites are regions where the membranes of neighbouring organelles are tethered in close proximity (typically 5-40nm apart) by protein and lipid complexes and are important sites of signaling and lipid and ion exchange. Our data suggest that MLCs are heavily influenced by the LE/Lys lipid environment, identifying a direct correlation between MLC extent and LE/Lys cholesterol levels. Expanded MLCs in NPC are associated with mitochondrial lipid accumulation, likely contributing to mitochondrial dysfunction, exacerbated by impaired removal of damaged mitochondria by mitophagy when MLCs are increased.
The lab is also exploring ER contact sites with lysosomes and lysosome-related organelles and applying findings from NPC to other diseases including Age-related Macular Degeneration and Parkinson’s Disease.
Date:
3 February 2026, 12:00
Venue:
Pharmacology, off Mansfield Road OX1 3QT
Venue Details:
David Smith Lecture Theatre
Speaker:
Associate Professor Emily Eden (Institute of Opthamology, UCL/Department of Pharmacology)
Organising department:
Department of Pharmacology
Organiser:
Carolyn Thackrah (University of Oxford, Department of Pharmacology)
Organiser contact email address:
carolyn.thackrah@pharm.ox.ac.uk
Host:
Professor Antony Galione (Department of Pharmacology, University of Oxford)
Part of:
Pharmacology, Anatomical Neuropharmacology and Drug Discovery Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Carolyn Thackrah
