Rab11a-dependent recycling of Glut3 inhibits seizure-induced neuronal disulfidptosis by alleviating glucose deficiency.

Abstract

Seizures can trigger neuronal glucose deficiency, thereby inducing disulfidptosis. Disulfidptosis is a novel cell death mechanism characterized by the abnormal accumulation of disulfide caused by glucose deficiency. However, the mechanism underlying disulfidptosis caused by glucose deficiency in seizures remains elusive. Rab11a-dependent recycling of glucose transporter 3 (Glut3) is closely related to glucose metabolism in neurons, which may contribute to neuronal disulfidptosis after seizures by abnormal glucose metabolism. So here we introduced a well-established in vitro model of seizures to evaluate cell survival, glucose levels, disulfidptosis biomarkers, Glut3 and Rab11a expression, the recycling ratio of Glut3, and the protein complex of Glut3-Rab11a. Cell survival rates and glucose levels were lower in the in vitro model of seizures, accompanied by elevated levels of disulfidptosis markers. Moreover, the surface expression and the recycling ratio of Glut3, as well as the protein complex of Glut3-Rab11a, were positively correlated with Rab11a expression. Lastly, Rab11 overexpression improved cell survival rates, increased glucose levels, and decreased the levels of disulfidptosis biomarkers in the in vitro model of seizure. Rab11a-dependent recycling of Glut3 inhibited seizure-induced neuronal disulfidptosis by alleviating glucose deficiency.