Connecting Mitochondria, Metabolism, and Stem Cell Fate

Abstract

As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases.

Human treated dentin matrices combined with Zn-doped, Mg-based bioceramic scaffolds and human dental pulp stem cells towards targeted dentin regeneration

“…4C). The downregulation of the metabolic-based MTT values at day 15 might be related to mitochondria bioenergetics and metabolic shifts occurring during somatic stem cell differentiation in culture, as supported in previous studies showing controversial results [21] and needs further investigation. The scaffolds also proved potent at inducing pronounced up-regulation of odontogenesis-related genes, especially DSPP and BMP-2, without exogenous addition of inductive factors, such as dexamethasone normally necessary to induce odontogenic differentiation of MSCs grown as monolayers [20].…”

Cap-independent translation by DAP5 controls cell fate decisions in human embryonic stem cells

“…Moreover, the glycolytic intermediate acetyl-CoA is used for histone acetylation, an epigenetic mechanism for maintaining pluripotency (Moussaieff et al 2015). Differentiation of stem cells is accompanied by enhanced mitochondrial biogenesis and oxidative respiration as well as elongation of mitochondria into a mature network, changes that occur even before loss of pluripotent markers (Mandal et al 2011;Wanet et al 2015). Significantly, we show here that inhibition of specific components of the oxidative phosphorylation pathway blocked RA-induced differentiation, consistent with similar inhibition studies during spontaneous differentiation of ESCs (Varum et al 2009;Mandal et al 2011;Zhang et al 2011;Pereira et al 2013), indicating that oxidative respiration is required for proper differentiation.…”

A clickable glutathione approach for identification of protein glutathionylation in response to glucose metabolism

“…1-3 Mitochondrial metabolism depends on various intracellular and extracellular conditions, including nutrient availability and oxygen concentrations. One of major nutrients is glucose that is degraded via glycolysis to pyruvate, which is further catabolized by Krebs cycle and oxidative phosphorylation in mitochondria for production of ATP.…”