For example, accumulation of EMRE protein in the absence of mitochondrial AAA-proteases AFG3L2 and SPG7, whose mutations are associated with spinocerebellar ataxia and hereditary spastic paraplegia, is responsible for mitochondrial Ca2+ overload and may contribute to neuronal loss (Konig et al, 2016). This evidence concerns the gene SMDT1 and hereditary spastic paraplegia.