RRC ID 36194
Author Nakatsukasa K, Nishimura T, Byrne SD, Okamoto M, Takahashi-Nakaguchi A, Chibana H, Okumura F, Kamura T.
Title The Ubiquitin Ligase SCF(Ucc1) Acts as a Metabolic Switch for the Glyoxylate Cycle.
Journal Mol. Cell
Abstract Despite the crucial role played by the glyoxylate cycle in the virulence of pathogens, seed germination in plants, and sexual development in fungi, we still have much to learn about its regulation. Here, we show that a previously uncharacterized SCF(Ucc1) ubiquitin ligase mediates proteasomal degradation of citrate synthase in the glyoxylate cycle to maintain metabolic homeostasis in glucose-grown cells. Conversely, transcription of the F box subunit Ucc1 is downregulated in C2-compound-grown cells, which require increased metabolic flux for gluconeogenesis. Moreover, in vitro analysis demonstrates that oxaloacetate regenerated through the glyoxylate cycle induces a conformational change in citrate synthase and inhibits its recognition and ubiquitination by SCF(Ucc1), suggesting the existence of an oxaloacetate-dependent positive feedback loop that stabilizes citrate synthase. We propose that SCF(Ucc1)-mediated regulation of citrate synthase acts as a metabolic switch for the glyoxylate cycle in response to changes in carbon source, thereby ensuring metabolic versatility and flexibility.
Volume 59(1)
Pages 22-34
Published 2015-7-2
DOI 10.1016/j.molcel.2015.04.013
PII S1097-2765(15)00269-5
PMID 25982115
MeSH Cell Cycle / genetics Citrate (si)-Synthase / metabolism* F-Box Proteins / metabolism Glucose / metabolism Glyoxylates / metabolism Neoplasm Proteins / biosynthesis* Neoplasm Proteins / genetics Nerve Tissue Proteins / biosynthesis* Nerve Tissue Proteins / genetics Oxaloacetic Acid / metabolism Proteasome Endopeptidase Complex / metabolism SKP Cullin F-Box Protein Ligases / metabolism* Saccharomyces cerevisiae / metabolism* Transcription, Genetic / genetics Ubiquitination
IF 14.248
Times Cited 5
Yeast BYP1804