Abstract
Mitochondria are considered highly plastic organelles. This plasticity enables the mitochondria to undergo morphological and functional changes in response to cellular demands. Stem cells also need to remain functionally plastic (i.e. to have the ability to "decide" whether to remain quiescent or to undergo activation upon signaling cues to support tissue function and homeostasis). Mitochondrial plasticity is thought to enable this reshaping of stem cell functions, integrating signaling cues with stem cell outcomes. Indeed, recent evidence highlights the crucial role of maintaining mitochondrial plasticity for stem cell biology. For example, tricarboxylic acid (TCA) cycle metabolites generated and metabolized in the mitochondria serve as cofactors for epigenetic enzymes, thereby coupling mitochondrial metabolism and transcriptional regulation. Another layer of mitochondrial plasticity has emerged, pointing toward mitochondrial dynamics in regulating stem cell fate decisions. Imposing imbalanced mitochondrial dynamics by manipulating the expression levels of the key molecular regulators of this process influences cellular outcomes by changing the nuclear transcriptional program. Moreover, reactive oxygen species have also been shown to play an important role in regulating transcriptional profiles in stem cells. In this review, we focus on recent findings demonstrating that mitochondria are essential regulators of stem cell activation and fate decisions. We also discuss the suggested mechanisms and alternative routes for mitochondria-to-nucleus communications.
Highlights
As mitochondrial regulation of stem cell function is becoming increasingly recognized, mitochondrial metabolism in particular was shown to have a pivotal role in dictating whether a stem cell will proliferate, differentiate, or remain quiescent [7]
The abundance and availability of TCA3 cycle metabolites, that function as epigenetic enzyme cofactors, reshape DNA and histones to establish an epigenetic landscape to initiate nuclear transcriptional reprogramming (8 –10)
Terminally differentiated cells shift their reliance of bioenergetic demands to the mitochondria by utilizing oxidative phosphorylation (OXPHOS), the process of energy generation fueled by respiration and the electron transport chain (ETC), characterized by a hyperfused mitochondrial network important for OXPHOS activity [17]
Summary
Tricarboxylic acid (TCA) cycle metabolites generated and metabolized in the mitochondria serve as cofactors for epigenetic enzymes, thereby coupling mitochondrial metabolism and transcriptional regulation Another layer of mitochondrial plasticity has emerged, pointing toward mitochondrial dynamics in regulating stem cell fate decisions. Terminally differentiated cells shift their reliance of bioenergetic demands to the mitochondria by utilizing oxidative phosphorylation (OXPHOS), the process of energy generation fueled by respiration and the ETC, characterized by a hyperfused mitochondrial network important for OXPHOS activity [17] These metabolic shifts are accompanied by profound changes in mitochondria morphology, and mitochondrial dynamics and metabolism were shown to reciprocally influence each other during cellular processes [5, 18]. We discuss the evolving mitochondrial mechanisms for self-renewal and stem cell differentiation, mainly focusing on mitochondrial dynamics, cellular metabolic programming, and epigenetic remodeling, placing the mitochondria at the center of stem cell fate decisions
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
