title: Mitochondrial DNA 3243A>G mutation and increased expression of LARS2 gene in the brains of patients with bipolar disorder and schizophrenia.
abstract: BACKGROUND
  Accumulating evidence suggests mitochondrial dysfunction in bipolar disorder. Analyses of mitochondria-related genes using DNA microarray showed significantly increased LARS2 (mitochondrial leucyl-tRNA synthetase) in the postmortem prefrontal cortices of patients with bipolar disorder provided by the Stanley Foundation Brain Collection. LARS2 is a nuclear gene encoding the enzyme catalyzing the aminoacylation of mitochondrial tRNA(Leu). A well-studied mitochondrial DNA point mutation, 3243A>G, in the region of tRNA(Leu (UUR)), related with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), is known to decrease the efficiency of aminoacylation of tRNA(Leu (UUR)).
  
  
  METHODS
  The steady state level of LARS2 was examined in the transmitochondrial cybrids carrying 3243A>G. We examined the 3243A>G mutation in these brains using the peptide nucleic acid-clamped polymerase chain reaction restriction fragment length polymorphism method.
  
  
  RESULTS
  LARS2 was upregulated in the transmitochrondrial cybrids carrying 3243A>G. The 3243A>G was detected in the postmortem brains of two patients with bipolar disorder and one with schizophrenia. These patients also showed higher levels of the mutation in their livers and significantly higher gene expression of LARS2 compared with other subjects.
  
  
  CONCLUSIONS
  These results suggest that upregulation of LARS2 is a hallmark of 324A>G mutation. The accumulation of 3243A>G mutation in the brain may have a pathophysiologic role in bipolar disorder and schizophrenia.
authors.affiliation: Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Kae
authors.initials: K
authors.lastname: Munakata
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwamoto
authors.forename: Miki
authors.initials: M
authors.lastname: Bundo
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000096:biosynthesis; D012356:RNA, Transfer, Leu / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D012356:RNA, Transfer, Leu