Cellular autophagy, an unbidden effect of caspase inhibition by zVAD-fmk.

Dharaniya Sakthivel, Beatriz E Bolívar, Lisa Bouchier-Hayes

The FEBS journal 2022 Jun

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zVAD-fmk is a widely used pan-caspase inhibitor that blocks apoptosis but has undesirable side effects, including autophagy. In this issue, Needs et al. propose that zVAD-fmk induces autophagy by inhibiting the N-glycanase NGLY1 rather than caspases. NGLY1 is essential for the ERAD response and patients with inactivating mutations in NGLY1 present with neurodevelopmental defects and organ dysfunction. The ability of NGLY1 to inhibit basal levels of autophagy may contribute to this pathology. This study demonstrates possible crosstalk between protein turnover and autophagy while also underscoring the importance of specificity when using chemical tools to interrogate these pathways. Comment on https://doi.org/10.1111/febs.16345. © 2022 Federation of European Biochemical Societies.

Citation

Dharaniya Sakthivel, Beatriz E Bolívar, Lisa Bouchier-Hayes. Cellular autophagy, an unbidden effect of caspase inhibition by zVAD-fmk. The FEBS journal. 2022 Jun;289(11):3097-3100