Regulated spatial organization and sensitivity of cytosolic protein oxidation in Caenorhabditis elegans

Nat Commun. 2014 Sep 29;5:5020. doi: 10.1038/ncomms6020.

Abstract

Cells adjust their behaviour in response to redox events by regulating protein activity through the reversible formation of disulfide bridges between cysteine thiols. However, the spatial and temporal control of these modifications remains poorly understood in multicellular organisms. Here we measured the protein thiol-disulfide balance in live Caenorhabditis elegans using a genetically encoded redox sensor and found that it is specific to tissues and is patterned spatially within a tissue. Insulin signalling regulates the sensor's oxidation at both of these levels. Unexpectedly, we found that isogenic individuals exhibit large differences in the sensor's thiol-disulfide balance. This variation contrasts with the general view that glutathione acts as the main cellular redox buffer. Indeed, our work suggests that glutathione converts small changes in its oxidation level into large changes in its redox potential. We therefore propose that glutathione facilitates the sensitive control of the thiol-disulfide balance of target proteins in response to cellular redox events.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Cysteine / chemistry
  • Cytosol / metabolism*
  • Disulfides / chemistry
  • Gene Expression Regulation*
  • Glutathione / chemistry
  • Insulin / metabolism
  • Microscopy, Fluorescence
  • Oxidation-Reduction
  • Oxygen / chemistry*
  • Pharynx / physiology
  • Signal Transduction
  • Sulfhydryl Compounds / chemistry
  • Transgenes

Substances

  • Disulfides
  • Insulin
  • Sulfhydryl Compounds
  • Glutathione
  • Cysteine
  • Oxygen