Fig. 8: Schematic diagram of TTK regulation of mitophagy. | Cell Death & Differentiation

Fig. 8: Schematic diagram of TTK regulation of mitophagy.

From: TTK promotes mitophagy by regulating ULK1 phosphorylation and pre-mRNA splicing to inhibit mitochondrial apoptosis in bladder cancer

Fig. 8

In BC cells with high TTK expression, TTK phosphorylates ULK1 at the Ser477 site, which subsequently phosphorylates FUNDC1 at the Ser17 site, inducing mitophagy. TTK also phosphorylates SRSF3 at the Ser108 site, preventing ULK1 exon 5 skipping and maintaining ULK1 mRNA stability, thereby increasing ULK1 protein expression. These processes promote high levels of mitophagy, enhancing BC cells survival under conditions such as oxidative stress or hypoxia. When TTK is knocked down, phosphorylation of ULK1 at Ser477 is reduced, inhibiting mitophagy and leading to the accumulation of damaged mitochondria and excessive mtROS production, promoting mitochondrial apoptosis. TTK knockdown also facilitates ULK1 exon 5 skipping, triggering the NMD pathway, reducing ULK1 mRNA and protein levels, further decreasing mitophagy, and accelerating BC cells mitochondrial apoptosis.

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