Exploring the use of Raman microscopy to determine mitochondrial function and mitochondrial drug accumulation in aging model systems

Active: 2020.01.01 - 2021.09.30
UK SPINE Scientific Liaison: Monica Spisar

Metabolic dysfunction is a key pathway in ageing, and mitochondria are important regulators of cellular metabolism. This work aims to establish a sensitive, label-free method for characterizing the impact of an individual drug on mitochondrial function to support discovery and development of therapeutic interventions for ageing acting via this biological pathway. Furthermore, this method will enable a more complete understanding of mechanisms of action of existing such interventions and may generate supplemental information regarding toxicity.

Direct effects of drugs on mitochondria are difficult to study; there is currently no label-free method for interrogating mitochondrial function or visualizing mitochondria in cells, and existing methods lack sensitivity. This work will explore the potential of Raman spectroscopy to measure and visualize mitochondrial uptake of drugs and their subsequent functional impact on in vitro (dopaminergic neurons, Werner’s and NPC) and in vivo (young (8 week) and old (24 week) mice) models of ageing.

Raman spectroscopy will be used to determine if existing drugs of relevance to mitigating ageing have unique spectra and to visualize mitochondria in live cells. Those results will be combined to establish co-localisation of drugs in isolated mitochondria and in live cells, and to characterize, at the single cell and bulk culture level, changes in mitochondrial function in response to drugs.

This work involves collaboration with an industry partner; in addition to the various scientific outputs of relevance to drug discovery, results will support the integration of Raman spectroscopy into commercially available systems for high throughput drug screens.

*Note: The subset of existing drugs of relevance to mitigating ageing included in this study:
Rapamycin, Nicotinamide, Ursodeoxycholic Acid, Curcumin, NBS037 (MT) (Novintum Biotech GmbH compound), Doxycycline (MT), Urolitherin A, Tanganil[N-acetyl-dl-leucine], Reservatrol, Bezafibrate, Metformin/Phenformin, Quercitin, Coenzyme Q10, Valproic acid, Honokiol
(‘MT’ indicates the drug is known to directly target mitochondria; the other compounds affect mitochondrial function but mitochondrial localization is unconfirmed.)