Open AccessDopamine signaling impairs ROS modulation by mitochondrial hexokinase in human neural progenitor cells
Author(s) -
Gabriela Assis-de-Lemos,
Jamila Monteiro,
Viviane M. Oliveira-Valença,
Guilherme A Melo,
Ricardo Augusto de Melo Reis,
Stevens K. Rehen,
Mariana S. Silveira,
Antônio Galina
Publication year - 2021
Publication title -
bioscience reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.938
H-Index - 77
eISSN - 1573-4935
pISSN - 0144-8463
DOI - 10.1042/bsr20211191
Subject(s) - neural stem cell , mitochondrion , dopamine , microbiology and biotechnology , biology , reactive oxygen species , progenitor cell , signal transduction , mitochondrial ros , dopaminergic , induced pluripotent stem cell , neuroscience , chemistry , stem cell , biochemistry , embryonic stem cell , gene
Dopamine signaling has numerous roles during brain development. In addition, alterations in dopamine signaling may be also involved in the pathophysiology of psychiatric disorders. Neurodevelopment is modulated in multiple steps by reactive oxygen species (ROS), byproducts of oxidative metabolism that are signaling factors involved in proliferation, differentiation, and migration. Hexokinase (HK), when associated with the mitochondria (mt-HK), is a potent modulator of the generation of mitochondrial ROS in the brain. In the present study, we investigated whether dopamine could affect both the activity and redox function of mt-HK in human neural progenitor cells (NPCs). We found that dopamine signaling via D1R decreases mt-HK activity and impairs ROS modulation, which is followed by an expressive release of H2O2 and impairment in calcium handling by the mitochondria. Nevertheless, mitochondrial respiration is not affected, suggesting specificity for dopamine on mt-HK function. In neural stem cells (NSCs) derived from induced-pluripotent stem cells (iPSCs) of schizophrenia patients, mt-HK is unable to decrease mitochondrial ROS, in contrast with NSCs derived from healthy individuals. Our data point to mitochondrial hexokinase as a novel target of dopaminergic signaling, as well as a redox modulator in human neural progenitor cells, which may be relevant to the pathophysiology of neurodevelopmental disorders such as schizophrenia.