“…For instance, the p.S59L variant reported in patients with ALS-FTD (frontotemporal dementia) is associated with a fragmented mitochondrial network, protein aggregates in mitochondria, and the activation of the integrated stress response (ISR), ascribed to a toxic gain of function (Anderson, Bredvik et al, 2019, Genin, Bannwarth et al, 2018, Genin, Madji Hounoum et al, 2019. On the other hand, the p.R15L and p.G66V variants, in which reduced levels of CHCHD10 protein are associated with mitochondrial respiratory chain dysfunction, appear to be haploinsufficient (Brockmann, Freischmidt et al, 2018, Penttila, Jokela et al, 2015, Straub et al, 2018.…”