Toxic effects of expanded ataxin-1 involve mechanical instability of the nuclear membrane

► One of the mechanisms causing SCA1 neurodegeneration could involve membrane destabilization. ► We analyzed the interaction between normal or expanded ataxin 1 and lipid membranes. ► Morphological analyses revealed nuclear membrane damage of cells expressing toxic ataxin 1. ► Atomic force microscopy and electrophysiology showed increased membrane fragility and permeability. ► We suggest that expanded ataxin 1 induces unregulated ionic pathways in the nuclear membrane.