The body's power plants are being probed by a multidisciplinary collaboration of UK scientists. 

Mitochondria are the energy power houses of cells, generating the ATP (adenosine triphosphate) used as fuel in biological processes. Yet, despite their importance, mysteries still surround how mitochondria work. Scientists investigating these structures often treat them with AG10, a compound that destroys mitochondrial activity, allowing their function to be studied. But AG10 acts indiscriminately throughout a cell. Now, researchers at the Universities of Oxford, Strathclyde and St Andrews have modified AG10 to generate a new spatially-selective mitochondrial probe. 

AG10 (black) is released from its nitrobenzyl cage (red) on treatment with laser light

The probe works thanks to a nitrobenzyl 'cage' group attached to a phenol group on AG10. The cage prevents AG10 exerting its biologically active properties, that is until laser light is applied to unlock the cage. 'The advantage of this is two fold,' says Stuart Conway who led the collaboration with John McCarron. 'Not only can we decide when to release these compounds but we can also decide where we release them.' 

By testing the caged compound in muscle cells the researchers demonstrated that laser photolysis releases caged AG10 only in regions of the cell near the photolysis site, enabling AG10 to go on to locally knock-out mitochondrial activity.

'The key benefit of the work is in providing chemical tools that offer the prospect of high-resolution investigation of mitochondrial function for the first time,' says James Dowden, an expert in the design and synthesis of chemical probes for biological systems, from the University of Nottingham, UK. 

The UK team says it expects the probe to allow researchers to look at the role mitochondria play in calcium signalling, an integral part of many physiological processes, including learning and memory, in more detail than ever before. Towards this, they now plan to apply the cage concept to investigate protein complexes involved in an intracellular messenger system linked to calcium signalling. 

Jennifer Newton

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