8GR9

Crystal structure of peroxisomal citrate synthase (Cit2) from Saccharomyces cerevisiae in complex with oxaloacetate and coenzyme-A

Summary for 8GR9

• Entry DOI: 10.2210/pdb8gr9/pdb
• Related: 8GQZ
• Descriptor: Citrate synthase, COENZYME A, GLYCEROL, ... (7 entities in total)
• Functional Keywords: glyoxylate cycle, peroxisomal protein, citrate metabolism, scfucc1 ubiquitin ligase, proteasome-dependent degradation, transferase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Total number of polymer chains: 2
• Total formula weight: 104350.77

Authors

Nishio, K.,Nakatsukasa, K.,Kamura, T.,Mizushima, T. (deposition date: 2022-09-01, release date: 2023-04-26, Last modification date: 2024-05-29)

Primary citation

Nishio, K.,Kawarasaki, T.,Sugiura, Y.,Matsumoto, S.,Konoshima, A.,Takano, Y.,Hayashi, M.,Okumura, F.,Kamura, T.,Mizushima, T.,Nakatsukasa, K.
Defective import of mitochondrial metabolic enzyme elicits ectopic metabolic stress.
Sci Adv, 9:eadf1956-eadf1956, 2023

PubMed Abstract: Deficiencies in mitochondrial protein import are associated with a number of diseases. However, although nonimported mitochondrial proteins are at great risk of aggregation, it remains largely unclear how their accumulation causes cell dysfunction. Here, we show that nonimported citrate synthase is targeted for proteasomal degradation by the ubiquitin ligase SCF. Unexpectedly, our structural and genetic analyses revealed that nonimported citrate synthase appears to form an enzymatically active conformation in the cytosol. Its excess accumulation caused ectopic citrate synthesis, which, in turn, led to an imbalance in carbon flux of sugar, a reduction of the pool of amino acids and nucleotides, and a growth defect. Under these conditions, translation repression is induced and acts as a protective mechanism that mitigates the growth defect. We propose that the consequence of mitochondrial import failure is not limited to proteotoxic insults, but that the accumulation of a nonimported metabolic enzyme elicits ectopic metabolic stress.

PubMed: 37058555
DOI: 10.1126/sciadv.adf1956

Experimental method

X-RAY DIFFRACTION (1.48 Å)