Fig. 10: Model for OSP-1 neuroprotection against acute oxidative stress.
From: OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress
We propose that OSP-1 functions at the ER as a negative regulator of autophagy. Mutations in OSP-1 (OSP-1-/-; top section) lead to decreased ER branching in the axonal proximal segment and an increase of lysosomes in the cell body with clustering between the soma and the axon, which is associated with higher autophagy; this results in enhanced oxidative stress-induced autophagy-dependent cell death, compared to wild-type (middle section). In contrast, OSP-1 overexpression (bottom section) causes a rearrangement of the ER towards the proximal region of the axon, accompanied by a dispersion of lysosomes from the cell body towards the neurite, with consequent reduction of autophagy and reduced cell death. Created in BioRender. Ritchie, F. (2024) https://BioRender.com/d57p325.
