Author:

Abstract:

Membrane lesions occur constantly within a cell and have to be efficiently repaired to prevent further damage. It has been recently shown that the endosomal sorting complexes required for transport (ESCRT) are able to repair lesions in the plasma membrane and the nuclear lamina (Jimenez et al., 2014; Sundquist and Ullman, 2015). ESCRT has been identified as a crucial factor for multivesicular body (MVB) formation and protein sorting, vesicular and cellular abscission and also for viral budding events. Especially the ESCRT-III accessory component ALIX (yeast Bro1) seems to play a crucial role in the lasts steps of membrane scission events (Johnson et al., 2017). We made use of a humanized yeast model expressing several mutants of the Alzheimer’s disease related protein amyloid β42 to show a direct link between the ESCRT-III accessory complex and Aβ42 induced cytotoxicity. Upon deletion of BRO1 (bro1Δ) toxicity of Aβ42 increases dramatically and Aβ42 expressing cells show a corrugated plasma membrane. Furthermore the level of reactive oxygen species (ROS) are significantly elevated in bro1Δ cells. Intriguingly, Aβ42 localizes at mitochondria, the main source of intracellular reactive oxygen species, in these cells. Based on these results we propose a model in which Aβ42 induces membrane lesions and that cells need the ESCRT-III factor Bro1 in order to repair this damage.