biostudies-otherUnknownProf. Massimo ZevianiEC | FP7 | FP7 Ideas: European Research Council (FP7 Ideas)Fondazione Telethon (Telethon Foundation)EMBO Molecular Medicinehttps://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMM-2018-09582Loss-of-function mutations in APOPT1, a gene exclusively found in higher eukaryotes, cause a characteristic type of cavitating leukoencephalopathy associated with mitochondrial cytochrome c oxidase (COX) deficiency. Although the genetic association of APOPT1 pathogenic variants with isolated COX defects is now clear, the biochemical link between APOPT1 function and COX has remained elusive. We investigated the molecular role of APOPT1 using different approaches. First, we generated an Apopt1 knockout mouse model which shows impaired motor skills, e.g. decreased motor coordination and endurance, associated with reduced COX activity and levels in multiple tissues. In addition, by achieving stable expression of wild-type APOPT1 in control and patient-derived cultured cells we ruled out a rolebiostudies-otherGGP15091FP7-322424Anna, S DicksonDr. Elizabeth, C HinchyDr. Erika Fernandez-VizarraDr. Raffaele CeruttiJames, A NathanAlba SignesDr. Cristiane BenincàDr. Enrico, S BertiniMichael, P MurphyProf. Massimo ZevianiDr. Daniele GhezziDr. Rosalba CarrozzoDr. Carlo ViscomifalseAPOPT1/COA8 ASSISTS COX ASSEMBLY AND IS OPPOSITELY REGULATED BY UPS AND ROSLoss-of-function mutations in APOPT1, a gene exclusively found in higher eukaryotes, cause a characteristic type of cavitating leukoencephalopathy associated with mitochondrial cytochrome c oxidase (COX) deficiency. Although the genetic association of APOPT1 pathogenic variants with isolated COX defects is now clear, the biochemical link between APOPT1 function and COX has remained elusive. We investigated the molecular role of APOPT1 using different approaches. First, we generated an Apopt1 knockout mouse model which shows impaired motor skills, e.g. decreased motor coordination and endurance, associated with reduced COX activity and levels in multiple tissues. In addition, by achieving stable expression of wild-type APOPT1 in control and patient-derived cultured cells we ruled out a role2019-01-16T21:00:09Z2019-01-16T21:00:09Z2019-01-16T21:00:09ZS-SCDT-EMM-2018-0958210.15252/emmm.201809582