title: Pharmacological targeting of mitochondrial complex I deficiency: the cellular level and beyond.
abstract: Complex I (CI) represents a major entry point of electrons in the mitochondrial electron transport chain (ETC). It consists of 45 different subunits, encoded by the mitochondrial (mtDNA) and nuclear DNA (nDNA). In humans, mutations in nDNA-encoded subunits cause severe neurodegenerative disorders like Leigh Syndrome with onset in early childhood. The pathophysiological mechanism of these disorders is still poorly understood. Here we summarize the current knowledge concerning the consequences of nDNA-encoded CI mutations in patient-derived cells, present mouse models for human CI deficiency, and discuss potential treatment strategies for CI deficiency.
authors.affiliation: Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peggy
authors.initials: P
authors.lastname: Roestenberg
authors.forename: Ganesh R
authors.initials: GR
authors.lastname: Manjeri
authors.forename: Federica
authors.initials: F
authors.lastname: Valsecchi
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Peter H G M
authors.initials: PH
authors.lastname: Willems
authors.forename: Werner J H
authors.initials: WJ
authors.lastname: Koopman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000172:deficiency / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000235:genetics
chemical_list: D042967:Electron Transport Complex I