Cleavage of Beclin 1 by metacaspase 1 activates antiviral autophagy in plants.

Abstract

Beclin 1/ATG6 plays a critical role in the biogenesis of autophagosomes and various cellular processes, but how Beclin 1-dependent autophagy is activated in plants remains elusive. Here, we found that the cysteine protease metacaspase 1 (MC1) functions as a new positive regulator of autophagy and cleaves Beclin 1 behind residues R97 and R99 in tobacco (Nicotiana benthamiana). Genetic analysis further demonstrated that the MC1-Beclin 1 cleavage module is both necessary and sufficient for the activation of plant autophagy. Mechanistically, this cleavage releases the N-terminal fragment of Beclin 1 (aa 1-97) which exhibits intrinsic autophagy-inducing activity and is dependent on the PI3K complex. Moreover, the activated autophagy boosts broad-spectrum antiviral responses, while the barley stripe mosaic virus (BSMV)-encoded γb protein targets MC1 and suppresses MC1-mediated Beclin 1 cleavage to optimize viral infection. The cleavage of Beclin 1 is thought to abolish its autophagic function in mammals; however, our findings unveil a distinctive plant autophagy mechanism whereby Beclin 1 activation necessitates MC1-mediated cleavage to drive antiviral autophagy.