Human SOD1 is secreted via a conventional secretion pathway in Saccharomyces cerevisiae

Biochem Biophys Res Commun. 2023 Jul 23:666:101-106. doi: 10.1016/j.bbrc.2023.05.022. Epub 2023 May 5.

Abstract

Soluble proteins sorted through the secretory pathway contain an N-terminal signal peptide that induces their translocation into the endoplasmic reticulum (ER) from the cytosol. However, a few proteins that lack a signal peptide are still translocated into the ER, such as SOD1. SOD1 is a causative gene of amyotrophic lateral sclerosis (ALS). A relationship has been suggested between the secretion of SOD1 and the pathogenesis of ALS; however, the transport mechanism of SOD1 remains unclear. We herein report that SOD1 was translocated into the ER lumen through the translocon Sec61 and was then secreted extracellularly. The present results indicate the potential of suppressing the secretion of SOD1 as a therapeutic target for ALS.

Keywords: Endoplasmic reticulum; SOD1; Secretion; Signal peptide; Translocon; Yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis* / metabolism
  • Humans
  • Mutation
  • Protein Sorting Signals / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Secretory Pathway
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism

Substances

  • Superoxide Dismutase-1
  • Superoxide Dismutase
  • Protein Sorting Signals
  • SOD1 protein, human