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- W4224884123 abstract "A/J mouse is a typical animal model of age-related deafness. Previous studies have shown that the mice suffer from progressive hearing loss and degeneration of cochlear cells, and a variation of H55 N in citrate synthase (CS) causes about 40% the hearing loss. CS is a key enzyme in the tricarboxylic acid cycle, which is transported from cytoplasm to mitochondria after synthesis, sorted by the mitochondrial targeting sequence (MTS). To explore the mechanism of CS (H55 N) variation in affecting its function, HEI-OC1 cells were infected with lentivirus particles to express CS-Flag or CS(H55 N)-Flag. The results showed that H55 N variation in CS, as purified by co-immunoprecipitation, decreased the enzyme activity by about 50%. Confocal microscope co-localization indicated that the CS (H55 N) variation led to a decrement in its mitochondrial content. Western blot also showed the amount of CS(H55 N)-Flag was more than that of CS(WT)-Flag in the cytosol. The results suggest H55 N variation in CS lead to decrement of its enzyme activity and targeting transport to mitochondria. We therefore conclude that decrement in CS activity and mitochondrial delivery contributes to the degeneration of cochlear cells and thus the hearing loss in A/J mice." @default.
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- W4224884123 date "2022-07-01" @default.
- W4224884123 modified "2023-10-17" @default.
- W4224884123 title "H55 N variation in citrate synthase leads to decrement in the enzyme activity and transport rate to mitochondria in HEI-OC1 cells" @default.
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- W4224884123 doi "https://doi.org/10.1016/j.bbrc.2022.04.104" @default.
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