2025/01/02 by Alessandra Donato, Fiona K. Ritchie, Lili Lu +8 · 1 voice · 5 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Apoptosis #Autophagy #Autophagy in Disease and Therapy #Biochemistry #Biology #Caenorhabditis elegans #Cell biology #Endoplasmic Reticulum Stress and Disease #Endoplasmic reticulum #Gene #Genetics, Aging, and Longevity in Model Organisms #Medicine #Neurodegeneration #Neuroprotection #Neuroscience #Oxidative phosphorylation #Oxidative stress #Pathology #Programmed cell death #Reactive oxygen species #Unfolded protein response
paper · pdf · doi:10.1038/s41467-024-55105-0
published in Nature Communications 16(1), 300 (Nature Portfolio)
openalex publication_date 2025/01/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well as in stroke. However, our knowledge of the genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death is still very limited. Here, using Caenorhabditis elegans as a model system, combined with the optogenetic tool KillerRed to spatially and temporally control ROS generation, we identify a previously uncharacterized gene, oxidative stress protective 1 (osp-1), that protects C. elegans neurons from oxidative damage. Using rodent and human cell cultures, we also show that the protective effect of OSP-1 extends to mammalian cells. Moreover, we demonstrate that OSP-1 functions in a strictly cell-autonomous fashion, and that it localizes to the endoplasmic reticulum (ER) where it has an ER-remodeling function. Finally, we present evidence suggesting that OSP-1 may exert its neuroprotective function by influencing autophagy. Our results point to a potential role of OSP-1 in modulating autophagy, and suggest that overactivation of this cellular process could contribute to neuronal death triggered by oxidative damage.