Mitochondrial multifaceted dysfunction in schizophrenia; complex I as a possible pathological target.
Mitochondria are key players in various essential cellular processes beyond being the main energy supplier of the cell. Accordingly, they are involved in neuronal synaptic transmission, neuronal growth and sprouting and consequently neuronal plasticity and connectivity. In addition, mitochondria participate in the modulation of gene transcription and inflammation as well in physiological responses in health and disease. Schizophrenia is currently regarded as a neurodevelopmental disorder associated with impaired immune system, aberrant neuronal differentiation and abnormalities in various neurotransmitter systems mainly the dopaminergic, glutaminergic and GABAergic. Ample evidence has been accumulated over the last decade indicating a multifaceted dysfunction of mitochondria in schizophrenia. Indeed, mitochondrial deficit can be of relevance for the majority of the pathologies observed in this disease. In the present article, we overview specific deficits of the mitochondria in schizophrenia, with a focus on the first complex (complex I) of the mitochondrial electron transport chain (ETC). We argue that complex I, being a major factor in the regulation of mitochondrial ETC, is a possible key modulator of various functions of the mitochondria. We review biochemical, molecular, cellular and functional evidence for mitochondrial impairments and their possible convergence to impact in-vitro neuronal differentiation efficiency in schizophrenia. Mitochondrial function in schizophrenia may advance our knowledge of the disease pathophysiology and open the road for new treatment targets for the benefit of the patients.
Laboratory of Psychobiology, Department of Psychiatry, Rambam Health Care Campus, B. Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-IIT, Haifa, Israel. Electronic address: shachar@tx.technion.ac.il.
Dorit
D
Ben-Shachar
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D042967:Electron Transport Complex I / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D014150:Antipsychotic Agents; D042967:Electron Transport Complex I
Complex I; Mitochondria; Mitochondrial dynamics; Mitochondrial respiration; Neuronal differentiation; Schizophrenia