Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.
Mitochondrial dysfunction is commonly observed in bipolar disorder (BD) and schizophrenia (SCZ) and may be a central feature of psychosis. These illnesses are complex and heterogeneous, which is reflected by the complexity of the processes regulating mitochondrial function. Mitochondria are typically associated with energy production; however, dysfunction of mitochondria affects not only energy production but also vital cellular processes, including the formation of reactive oxygen species, cell cycle and survival, intracellular Ca(2+) homeostasis, and neurotransmission. In this review, we characterize the upstream components controlling mitochondrial function, including 1) mutations in nuclear and mitochondrial DNA, 2) mitochondrial dynamics, and 3) intracellular Ca(2+) homeostasis. Characterizing and understanding the upstream factors that regulate mitochondrial function is essential to understand progression of these illnesses and develop biomarkers and therapeutics.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario Federal University of Santa Maria, Santa Maria, RS, Brazil Both authors contributed equally to this article.
Alencar Kolinski
AK
Machado
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario Both authors contributed equally to this article.
Alexander Yongshuai
AY
Pan
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario Federal University of Pelotas, Pelotas, RS, Brazil.
Tatiane Morgana
TM
da Silva
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario.
Angela
A
Duong
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario Department of Psychiatry, University of Toronto, Toronto, Ontario Centre for Addiction and Mental Health, Toronto, Ontario ana.andreazza@utoronto.ca.
Ana Cristina
AC
Andreazza
D001714:Bipolar Disorder / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism*; D011618:Psychotic Disorders / Q000378:metabolism*
bipolar disorder; mitochondria; psychosis; schizophrenia