Fig. 8: Schematic diagram summarising the results. | Cell Death & Disease

Fig. 8: Schematic diagram summarising the results.

From: ISGylation of DRP1 closely balances other post-translational modifications to mediate mitochondrial fission

Fig. 8

ISGylation of DRP1 [more specifically phopho-DRP1 (S616)] renders it fission competent. Mitochondrial filamentation occurs due to lack of this post-transaltional modification (as in Alzheimer’s disease, AD scenario) or in the presence of SARS-CoV2 PLpro (a deISGylating enzyme); USP18 could also impart deISGylation in cells. DRP1 is primarily ISGylated by HERC5 leading to fission; Ubiquitin E3 ligases, like PARKIN, MITOL and TRIM25 ubiquitylate and degrade DRP1 to promote fusion. In AD reduced expression of HERC5 and TRIM25 results in compromised DRP1 ISGylation and activity.

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