Evidence implicating the candidate schizophrenia/bipolar disorder susceptibility gene G72 in mitochondrial function

Area of Science:

• Neuroscience
• Genetics
• Cell Biology

Background:

• G72 is a candidate susceptibility gene for psychiatric disorders like schizophrenia and bipolar disorder.
• The precise function of G72 has remained largely unknown.
• Previous studies proposed a functional interaction between G72 and D-amino acid oxidase (DAO).

Purpose of the Study:

• To elucidate the function of the G72 gene.
• To investigate the cellular mechanisms influenced by G72.
• To explore the potential role of G72 in neuronal development.

Main Methods:

• Analysis of G72 splicing isoforms, identifying LG72 as encoding a mitochondrial protein.
• Experimentation with mammalian cell lines and primary neurons to assess the impact of G72 levels on mitochondrial morphology.
• Evaluation of mitochondrial transmembrane potential and apoptosis markers.
• Assessment of dendritic arborization in immature primary neurons with altered G72 levels.
• Testing the proposed G72-DAO interaction in cell lines.

Main Results:

• The splicing isoform LG72 encodes a mitochondrial protein.
• Elevated G72 levels induce significant mitochondrial fragmentation in cell lines and neurons, independent of apoptosis or changes in mitochondrial potential.
• Increased G72 levels in immature neurons correlate with enhanced dendritic arborization.
• The functional interaction between G72 and DAO was not confirmed in the tested cell lines.

Conclusions:

• G72 is a mitochondrial protein that modulates mitochondrial morphology.
• G72 influences neuronal development, specifically dendritic arborization.
• The findings suggest a novel role for G72 in mitochondrial function and neuronal structure, distinct from its previously proposed interaction with DAO.