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

• Published in: Biochemical and biophysical research communications 2023-07, Vol.666, p.101-106
• Main Authors: Hosomi, Akira, Okachi, Chinatsu, Fujiwara, Yudai
• Format: Article
• Language: English
• Subjects: Amyotrophic Lateral Sclerosis - metabolism; Endoplasmic reticulum; Humans; Mutation; Protein Sorting Signals - genetics; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Secretion; Secretory Pathway; Signal peptide; SOD1; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Superoxide Dismutase-1 - genetics; Superoxide Dismutase-1 - metabolism; Translocon; Yeast
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2023.05.022

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. •Recombinant human SOD1 is translocated into the endoplasmic reticulum in budding yeast.•Translocated human SOD1 into the ER is secreted via secretory pathway.•The present study suggests the potential of suppressing the secretion of SOD1 as a therapeutic target for ALS.