title: Revisiting Mitochondrial Function and Metabolism in Pluripotent Stem Cells: Where Do We Stand in Neurological Diseases?
abstract: Pluripotent stem cells (PSCs) are powerful cellular tools that can generate all the different cell types of the body, and thus overcome the often limited access to human disease tissues; this becomes highly relevant when aiming to investigate cellular (dys)function in diseases affecting the central nervous system. Recent studies have demonstrated that PSC and differentiated cells show altered mitochondrial function and metabolic profiles and production of reactive oxygen species. This raises an emerging paradigm about the role of mitochondria in stem cell biology and urges the need to identify mitochondrial pathways involved in these processes. In this respect, this review focuses on the metabolic profile of PSC and how mitochondrial function can influence the reprogramming and differentiation processes. Indeed, both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) favor the glycolytic pathway as a major source of energy production over oxidative phosphorylation. PSC mitochondria are characterized by a spherical shape, low copy number of mitochondrial DNA, and a hyperpolarized state. Indeed, mitochondria appear to have a crucial role in reprogramming iPSC, in the maintenance of a pluripotent state, and in differentiation. Moreover, an increase in mitochondrial oxidative phosphorylation has to occur for differentiation to succeed. Therefore, in vitro differentiation of neural stem cells (NSCs) into neurons can be compromised if those mechanisms are impaired. Future research should shed light on how mitochondrial impairment occurring in pre differentiation neural stages (e.g., in NSC or premature neurons) may contribute for the etiopathogenesis of neurodevelopmental and neurological disorders.
authors.affiliation: Doctoral Programme in Experimental Biology and Biomedicine of the CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Institute for Interdisciplinary Research of the University of Coimbra (IIIUC), Coimbra, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Center for Neuroscience and Cell Biology, and Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal. acrego@cnc.uc.pt.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal. acrego@cnc.uc.pt.
authors.forename: A Cristina
authors.initials: AC
authors.lastname: Rego
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009422:Nervous System Diseases / Q000378:metabolism* / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: Embryonic stem cells; Energy metabolism; Glycolysis; Induced pluripotent stem (iPS) cells; Mitochondria; Neurodegenerative diseases; Neuropsychiatric disorders; Pluripotent stem cells