Tandem Mass Tag proteomics in CHCHD10 patient cells

Mutations in CHCHD10, coding for a mitochondrial intermembrane space protein, are a rare cause of autosomal dominant amyotrophic lateral sclerosis (ALS). Mutation-specific toxic gain of function or haploinsuffuciency models have been proposed to explain pathogenicity. To decipher the metabolic dysfunction associated with the haploinsufficient p.R15L variant we conducted a TMT labelling experiment. Fibroblasts with the CHCHD10 p.R15L variant (hereafter referred to as ‘patient’), were compared to the same cells expressing wild-type CHCHD10 cDNA (hereafter called ‘rescue’) under nutrient stress, in which galactose was substituted for glucose.