Genetically encoded redox sensor identifies the role of ROS in degenerative and mitochondrial disease pathogenesis

Neurobiol Dis. 2012 Jan;45(1):362-8. doi: 10.1016/j.nbd.2011.08.022. Epub 2011 Aug 25.

Abstract

Mitochondrial dysfunction plays an important role in the pathogenesis of neurodegenerative diseases, numerous other disease states and senescence. The ability to monitor reactive oxygen species (ROS) within tissues and over time in animal model systems is of significant research value. Recently, redox-sensitive fluorescent proteins have been developed. Transgenic flies expressing genetically encoded redox-sensitive GFPs (roGFPs) targeted to the mitochondria function as a useful in vivo assay of mitochondrial dysfunction and ROS. We have generated transgenic flies expressing a mitochondrial-targeted roGFP2, demonstrated its responsiveness to redox changes in cultured cells and in vivo and utilized this protein to discover elevated ROS as a contributor to pathogenesis in a characterized neurodegeneration mutant and in a model of mitochondrial encephalomyopathy. These studies identify the role of ROS in pathogenesis associated with mitochondrial disease and demonstrate the utility of genetically encoded redox sensors in Drosophila.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Drosophila melanogaster
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurons / metabolism
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism*

Substances

  • Reactive Oxygen Species