Damage control: new functions for the Arp2/3 complex and WHAMM in autophagy and lysosomal homeostasis

Macroautophagy is an intracellular degradation process that relies on autophagosomes and lysosomes to maintain cellular and organismal homeostasis. Actin cytoskeletal rearrangements driven by the Arp2/3 (actin-related protein 2/3) complex, an essential actin nucleator, impact multiple steps of this pathway, but where and when Arp2/3-mediated actin assembly is most influential has remained unclear. Recent work now shows that the Arp2/3 complex is crucial in the later stages of autophagy due to its function in maintaining lysosomal integrity. WHAMM (WASP homolog associated with actin, membranes, and microtubules) is the key nucleation-promoting factor that activates Arp2/3 at permeabilized lysosomes, uncovering new roles for actin, the Arp2/3 complex, and WHAMM in lysosomal damage responses.