Article Text

Download PDFPDF

P12 A novel model of cardiomyopathy reveals a tissue specific role for the complex i assembly factor ecsit
  1. T Nicol1,
  2. S Falcone1,
  3. A Blease1,
  4. C Scudamore1,
  5. J Hirst2,
  6. C Viscomi2,
  7. M Zeviani2,
  8. SDM Brown1,
  9. PK Potter1
  1. 1Medical Research Council Harwell Institute, Harwell, Oxfordshire
  2. 2Medical Research Council Mitochondrial Biology Unit, Cambridge


Here we present a mouse model with a missense mutation in the gene Ecsit that shows a progressive cardiomyopathy from 4 weeks of age with no other overt phenotypes. ECSIT is known to play a role in development and immune signalling but is also thought to function as an assembly factor of complex I.

Western blot analysis of tissue lysates revealed a significant reduction in complex I proteins in heart tissue, whereas all other complexes were unaffected. In addition, Seahorse analysis of isolated mitochondria shows a significant reduction in the respiration rates of cardiac mitochondria, whilst no differences could be seen in mitochondria isolated from brain tissue.

In-gel activity demonstrated a significant drop in complex I activity of cardiac mitochondria, whilst brain mitochondria are maintained at close to normal levels. Blue native PAGE performed on cardiac mitochondria shows that this mutation affects ECSIT’s role in a limited number of complex I sub-assemblies. However, this is unique to the heart and mitochondria from brain tissue show no changes in any of the same sub-assemblies, supporting the initial findings that there is normal complex I assembly in the brain.

A potential mechanism lies in the discovery of a previously undescribed 16 kDa fragment of ECSIT that is present in WT cardiac mitochondria but not in mutant. This fragment is also undetectable in mitochondria isolated from brain tissue, indicating a tissue specific cleavage of ECSIT protein as a method of action.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.