title: Restoration of complex V deficiency caused by a novel deletion in the human TMEM70 gene normalizes mitochondrial morphology.
abstract: We report a fragmented mitochondrial network and swollen and irregularly shaped mitochondria with partial to complete loss of the cristae in fibroblasts of a patient with a novel TMEM70 gene deletion, which could be completely restored by complementation of the TMEM70 genetic defect. Comparative genomics analysis predicted the topology of TMEM70 in the inner mitochondrial membrane, which could be confirmed by immunogold labeling experiments, and showed that the TMEM70 gene is not restricted to higher multi-cellular eukaryotes. This study demonstrates that the role of complex V in mitochondrial cristae morphology applies to human mitochondrial disease pathology.
authors.affiliation: Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Laboratory for Genetic, Endocrine, and Metabolic Disorders, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
authors.forename: An I
authors.initials: AI
authors.lastname: Jonckheere
authors.forename: Merei
authors.initials: M
authors.lastname: Huigsloot
authors.forename: Martin
authors.initials: M
authors.lastname: Lammens
authors.forename: Jitske
authors.initials: J
authors.lastname: Jansen
authors.forename: Lambert P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
authors.forename: Jürgen-Christoph
authors.initials: JC
authors.lastname: von Kleist-Retzow
authors.forename: Marleen
authors.initials: M
authors.lastname: Forkink
authors.forename: Werner J H
authors.initials: WJ
authors.lastname: Koopman
authors.forename: Radek
authors.initials: R
authors.lastname: Szklarczyk
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Huynen
authors.forename: Jack A
authors.initials: JA
authors.lastname: Fransen
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Richard J T
authors.initials: RJ
authors.lastname: Rodenburg
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency*; D002352:Carrier Proteins; D002478:Cells, Cultured; D005347:Fibroblasts / Q000648:ultrastructure; D005816:Genetic Complementation Test; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D008928:Mitochondria / Q000648:ultrastructure*; D024101:Mitochondrial Proteins / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases; D017384:Sequence Deletion
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C533106:TMEM70 protein, human; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; C020439:oligomycin sensitivity-conferring protein