Maintaining Iron Homeostasis Is the Key Role of Lysosomal Acidity for Cell Proliferation.

ABSTRACT: The lysosome is an acidic multi-functional organelle with roles in macromolecular digestion, nutrient sensing, and signaling. However, why cells require acidic lysosomes to proliferate and which nutrients become limiting under lysosomal dysfunction are unclear. To address this, we performed CRISPR-Cas9-based genetic screens and identified cholesterol biosynthesis and iron uptake as essential metabolic pathways when lysosomal pH is altered. While cholesterol synthesis is only necessary, iron is both necessary and sufficient for cell proliferation under lysosomal dysfunction. Remarkably, iron supplementation restores cell proliferation under both pharmacologic and genetic-mediated lysosomal dysfunction. The rescue was independent of metabolic or signaling changes classically associated with

SUBMITTER: Weber RA 

PROVIDER: S-EPMC7176020 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature