The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes

The endoplasmic reticulum (ER) comprises morphologically and functionally distinct domains, sheets interconnected tubules. These domains undergo dynamic reshaping, in response to changes the cellular environment. However, mechanisms behind this rapid remodeling within minutes are largely unknown. Here, we report that ER is actively driven by lysosomes, following lysosome repositioning nutritional status. anchorage of lysosomes growth tips critical for tubule elongation connection. We validate causal link via chemo- optogenetically re-positioning which leads both a redistribution tubules its global morphology. Lysosomes sense metabolic change cell regulate distribution accordingly. Dysfunction mechanism during axonal extension may lead defects. Our results demonstrate role lysosome-regulated dynamics reshaping nutrient responses neuronal development.