title: Mitochondria in complex psychiatric disorders: Lessons from mouse models of 22q11.2 deletion syndrome: Hemizygous deletion of several mitochondrial genes in the 22q11.2 genomic region can lead to symptoms associated with neuropsychiatric disease.
abstract: Mitochondrial ATP synthesis, calcium buffering, and trafficking affect neuronal function and survival. Several genes implicated in mitochondrial functions map within the genomic region associated with 22q11.2 deletion syndrome (22q11DS), which is a key genetic cause of neuropsychiatric diseases. Although neuropsychiatric diseases impose a serious health and economic burden, their etiology and pathogenesis remain largely unknown because of the dearth of valid animal models and the challenges in investigating the pathophysiology in neuronal circuits. Mouse models of 22q11DS are becoming valid tools for studying human psychiatric diseases, because they have hemizygous deletions of the genes that are deleted in patients and exhibit neuronal and behavioral abnormalities consistent with neuropsychiatric disease. The deletion of some 22q11DS genes implicated in mitochondrial function leads to abnormal neuronal and synaptic function. Herein, we summarize recent findings on mitochondrial dysfunction in 22q11DS and extend those findings to the larger context of schizophrenia and other neuropsychiatric diseases.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Devaraju
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Zakharenko
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002892:Chromosomes, Human, Pair 22; D004062:DiGeorge Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: 22q11.2 deletion syndrome; ATP; calcium; mitochondria; schizophrenia; synapse; synaptic plasticity