Sugar coating autophagy: exploring the links between the inhibition of NGLY1 (N-glycanase 1) and autophagy induction

TL;DR

This paper explores how inhibiting the enzyme NGLY1 leads to the activation of autophagy, a cellular process that breaks down damaged components.

Contribution

The paper presents new evidence establishing a direct causal link between NGLY1 inhibition and autophagy induction.

Findings

Inhibiting NGLY1 leads to increased autophagy induction.

NGLY1 plays a key role in glycoprotein catabolism and ERAD pathway function.

Loss of NGLY1 function is linked to a rare congenital disorder with diverse symptoms.

Abstract

The cytosolic enzyme NGLY1 (N-glycanase 1) is a central mediator of glycoprotein catabolism. The enzyme acts to cleave N-linked glycans from modified substrate asparagine residues prior to degradation of misfolded proteins by the proteasome, playing a key and well-conserved role in the ER-associated degradation/ERAD pathway. In a clinical context, NGLY1 disorder represents a rare congenital disorder of deglycosylation where mutations in the NGLY1 gene result in the loss of enzyme function. Patients with NGLY1 disorder present with a broad and varied array of symptoms, which can include moderate to profound levels of developmental delay, seizures, and complex movement disorders, as well as alacrima. Our recent results highlight a causal link between NGLY1 inhibition and macroautophagy/autophagy induction.

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