title: The Ubiquitin Ligase SCF(Ucc1) Acts as a Metabolic Switch for the Glyoxylate Cycle.
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.
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan. Electronic address: z47875a@cc.nagoya-u.ac.jp.
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakatsukasa
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Byrne
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Chiba, 260-8673, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Chiba, 260-8673, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Takahashi-Nakaguchi
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Chiba, 260-8673, Japan.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Chibana
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Okumura
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan. Electronic address: z47617a@nucc.cc.nagoya-u.ac.jp.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kamura
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002950:Citrate (si)-Synthase / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D062907:Oxaloacetic Acid / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D054875:Ubiquitination; D036341:Intercellular Signaling Peptides and Proteins
chemical_list: D002950:Citrate (si)-Synthase; D044783:F-Box Proteins; D005947:Glucose; D006038:Glyoxylates; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D062907:Oxaloacetic Acid; D046988:Proteasome Endopeptidase Complex; D044843:SKP Cullin F-Box Protein Ligases; C456603:EPDR1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C031150:glyoxylic acid