CellSpex

• Research type

  Research Study

• Full title

  Multiwavelength cell spectroscopy to define the pathophysiology of mitochondrial disorders in living cells.

• IRAS ID

  147169

• Contact name

  Judy Hirst

• Contact email

  judy.hirst@mrc-mbu.cam.ac.uk

• Sponsor organisation

  Medical Research Council

• Research summary

  Mitochondria are the powerhouses of eukaryotic cells. Through oxidative phosphorylation (OxPhos), mitochondria extract energy from nutrients and use it to transfer protons across a proton-impermeable membrane creating a proton motive force to drive ATP production. Since the enzymes that catalyse OxPhos are encoded in both the mitochondrial and nuclear genomes, mutations in either one can cause mitochondrial disease, with a minimum prevalence of 1 in 5,000 live births in the EU. The molecular-biochemical causes of mitochondrial disorders and their clinical manifestations are highly diverse, but the most common defects are in complex I, the first enzyme of the OxPhos system. Currently, the mechanisms linking specific complex I mutations to OxPhos failure, cell and tissue damage, and ultimately disease, are poorly understood – precluding development of rational, evidence-based, therapies. The paucity of tools available to define mitochondrial function in the living cell is a major hindrance.
  This project employs recently developed technology that is capable of defining the bioenergetic status of mitochondria in living cells, with an exquisite level of accuracy, under tightly defined conditions. Every bioenergetic parameter that impacts on OxPhos function is accessible, including the redox potential of both substrates of complex I, the proton motive force, and the electron flux. Our goal is to define the functional consequences of mutations of complex I at the bioenergetic level to understand the aetiology of disease. This integrated approach will allow us to bridge fundamental gaps in knowledge, and drive forward the development of effective clinical therapies.

• REC name

  East Midlands - Nottingham 1 Research Ethics Committee

• REC reference

  14/EM/0041

• Date of REC Opinion

  14 Jan 2014

• REC opinion

  Favourable Opinion