Succinate Dehydrogenase loss causes cascading metabolic effects that impair pyrimidine biosynthesis.

ABSTRACT: Impaired availability of the amino acid aspartate can be a metabolic constraint of cell proliferation in diverse biological contexts. However, the kinetics of aspartate depletion, and its ramifications on downstream metabolism and cell proliferation, remain poorly understood. Here, we deploy the aspartate biosensor jAspSnFR3 with live cell imaging to resolve temporal relationships between aspartate and cell proliferation from genetic, pharmacological, and nutritional manipulations. In cells with impaired aspartate acquisition from mitochondrial complex I inhibition or constrained uptake in aspartate auxotrophs, we find that the proliferation defects lag changes in aspartate levels and only manifest once aspartate levels fall below a critical threshold, supporting the functional link betwee

SUBMITTER: Hart ML 

PROVIDER: S-EPMC11870577 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature