title: Mitochondrial complex I activity is significantly decreased in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with mitochondrial DNA C3310T mutation: a cybrid study.
abstract: Mitochondrial respiratory function in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with heteroplasmic mitochondrial DNA (mtDNA) C3310T mutation, which replaces the second amino acid of NADH dehydrogenase 1 (ND1) from a hydrophobic Proline to a hydrophilic Serine, was investigated. Mitochondrial respiratory function solely due to mtDNA C3310T mutation was investigated in cybrid system by the fusion of mtDNA-deleted (rho(0)) HeLa cells and exogenous mtDNA either from the proband or from controls. Total oxygen consumption of the proband cybrid cells was significantly decreased compared with those of controls (2.468+/-0.475 versus 2.871+/-0.484 micromol/h/10(7) cells, p=0.0392). Mitochondrial respiratory chain complex I activity of the proband cybrid cells was also significantly decreased compared with those of controls (0.191+/-0.080 versus 0.288+/-0.113 micromol/h/mg protein, p=0.0223). Furthermore, ATP content in the proband cybrid cells was also significantly decreased compared with those in controls (1.119+/-0.344 versus 1.419+/-0.378 pmol/10(5) cells, p=0.044). The present study indicates that mtDNA C3310T mutation may be a pathogenic mutation of maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy in the proband and the family.
authors.affiliation: Third Department of Internal Medicine, School of Medicine, University of Yamanashi, Tamaho, Yamanashi 409-3898, Japan.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hattori
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakajima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Eizawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ehara
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirai
authors.forename: Youji
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Onaya
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Masato
authors.initials: M
authors.lastname: Tawata
mesh_terms: D015139:Blotting, Southern; D002312:Cardiomyopathy, Hypertrophic / Q000201:enzymology / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010101:Oxygen Consumption; D020641:Polymorphism, Single Nucleotide
chemical_list: D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I