title: Using tuberous sclerosis complex to understand the impact of MTORC1 signaling on mitochondrial dynamics and mitophagy in neurons.
abstract: Constitutive activation of the MTOR pathway is a key feature of defects in the tuberous sclerosis complex and other genetic neurodevelopmental diseases, collectively referred to as MTORopathies. MTORC1 hyperactivity promotes anabolic cell functions such as protein synthesis, yet at the same time catabolic processes such as macroautophagy/autophagy are suppressed. Mitochondria are major substrates of autophagy; however, their role in MTORopathies remains largely undefined. Here, we review our recent study showing that several aspects of mitochondrial function, dynamics and turnover are critically impaired in neuronal models of TSC. We discuss the relevance of these findings to neurological manifestations associated with TSC and speculate on autophagy as a novel treatment target for MTORopathies.
authors.affiliation: a The F.M. Kirby Neurobiology Center , Department of Neurology , Boston Children's Hospital, Harvard Medical School , Boston , MA , USA.|b Division of Pediatric Neurology and Metabolic Medicine , Center for Child and Adolescent Medicine, University Hospital Heidelberg , Heidelberg , Germany.
authors.forename: Darius
authors.initials: D
authors.lastname: Ebrahimi-Fakhari
authors.affiliation: a The F.M. Kirby Neurobiology Center , Department of Neurology , Boston Children's Hospital, Harvard Medical School , Boston , MA , USA.|b Division of Pediatric Neurology and Metabolic Medicine , Center for Child and Adolescent Medicine, University Hospital Heidelberg , Heidelberg , Germany.
authors.forename: Afshin
authors.initials: A
authors.lastname: Saffari
authors.affiliation: b Division of Pediatric Neurology and Metabolic Medicine , Center for Child and Adolescent Medicine, University Hospital Heidelberg , Heidelberg , Germany.|c Division of Hematology and Oncology , Stem Cell Program, Boston Children's Hospital, Harvard Medical School , Boston , MA , USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Wahlster
authors.affiliation: a The F.M. Kirby Neurobiology Center , Department of Neurology , Boston Children's Hospital, Harvard Medical School , Boston , MA , USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sahin
mesh_terms: D000818:Animals; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D063306:Mitophagy; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction; D014402:Tuberous Sclerosis / Q000378:metabolism*
chemical_list: D000076222:Mechanistic Target of Rapamycin Complex 1
keywords: autism; autophagy; axonal transport; carbamazepine; lysosome; mTOR; mTORC1; mitochondria; rapamycin; synapse