Grant: CIHR Fellowship

Mitochondria are cellular organelles responsible for generating energy for human cells. The more energetically demanding a cell is, such as neurons, the more critical the health of mitochondria is. People with bipolar disorder experience mitochondrial defects. Alterations in the DNA sequence of a particular mitochondrial gene, called MT-ND2, were identified and may have a relevant impact on mitochondrial functions, decreasing the energy production of a cell, increasing levels of oxidative stress, and impairing neurotransmission. In the present study, we will adapt a method (transcription-activator-like effector (TALE)-linked deaminases) that will allow us to synthesize DNA sequences of the MT-ND2 gene containing either the desired variant G or control A in the position 4917, and incorporate the exogenous MT-ND2 into healthy and bipolar disorder patient-derived neurons. Thus, we will investigate the effects of the variant G on mitochondrial functions including energy production and levels of oxidative stress, as well as neurotransmission. Together, this work will provide critical insights into the functional significance of the variant G in the MT-ND2 gene in bipolar disorder and will establish a link between mitochondrial DNA variant, mitochondrial dysfunction and neuronal activity. The outcome of our findings could open new avenues to advance treatment for bipolar disorder.