Evidence implicating the candidate schizophrenia/bipolar disorder susceptibility gene G72 in mitochondrial function.
G72 is a strong candidate susceptibility gene for schizophrenia and bipolar disorder, whose function remains enigmatic. Here we show that one splicing isoform of the gene (LG72) encodes for a mitochondrial protein. We also provide convergent lines of evidence that increase of endogenous or exogenous G72 levels promotes robust mitochondrial fragmentation in mammalian cell lines and primary neurons, which proceeds in a manner that does not depend on induction of apoptosis or alteration in mitochondrial transmembrane potential. Finally, we show that increase in G72 levels in immature primary neurons is accompanied by a marked increase in dendritic arborization. By contrast, we failed to confirm the originally proposed functional interaction between G72 and D-amino acid oxidase (DAO) in two tested cell lines. Our results suggest an alternative role for G72 in modulating mitochondrial function.
Department of Physiology and Cellular Biophysics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
M
M
Kvajo
A
A
Dhilla
D E
DE
Swor
M
M
Karayiorgou
J A
JA
Gogos
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D001714:Bipolar Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000473:pathology / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000502:physiology; D009474:Neurons / Q000473:pathology; D011323:Primates / Q000235:genetics; D015183:Restriction Mapping; D012559:Schizophrenia / Q000235:genetics*
D002352:Carrier Proteins; C475071:DAOA protein, human; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins