Anxiety and mitochondria: Insights from the -omics world

Although the involvement of mitochondria in major psychiatric disorders has been repeatedly reported, limited information is available for mitochondrial alterations in anxiety disorders. In the present study, we developed a comprehensive and sensitive quantitative proteomics and metabolomics platform based on in vivo 15 N metabolic labeling and quantitative mass spectrometry to interrogate a mouse model of trait anxiety. We compared the cingulate cortex proteomes and metabolomes of high and low anxiety-related behavior mouse lines and investigated affected networks by in silico analysis. We identified differences in mitochondrial proteins, metabolites and pathways between high and low anxiety-related behavior mice and we validated selected changes by immunobased and enzymatic assays. Our data revealed alterations in mitochondrial import and transport, energy metabolism and oxidative stress in anxiety-related behavior. This work points towards a previously non-highlighted role of mitochondria in modulating anxiety-related behavior and provides insights towards novel therapeutic anxiety disorder targets at the organellar level.