Abstract

Simple SummaryStem cells are required to create all organs and tissues during development, as well as replace or regenerate tissues in adulthood. Stem cells are characterized by two main factors, which are (1) the ability to replenish themselves in order to maintain their population for further use, and (2) the ability to differentiate into specialized cells. These two characteristics are regulated by both external and internal factors. One of these internal factors is mitochondrial function. Mitochondria are organelles that serve an essential role to cells by providing energy and regulating cell survival. These organelles are now known to be important for allowing the stem cell characteristics. Given that proper mitochondrial function is crucial for cells, when they become defective they need to be removed. This process of removal, known as mitophagy or “mitochondrial eating”, is emerging as an important player in stem cells. In this review we discuss the new research that shows the importance of mitophagy in having functional stem cells.The fundamental importance of functional mitochondria in the survival of most eukaryotic cells, through regulation of bioenergetics, cell death, calcium dynamics and reactive oxygen species (ROS) generation, is undisputed. However, with new avenues of research in stem cell biology these organelles have now emerged as signaling entities, actively involved in many aspects of stem cell functions, including self-renewal, commitment and differentiation. With this recent knowledge, it becomes evident that regulatory pathways that would ensure the maintenance of mitochondria with state-specific characteristics and the selective removal of organelles with sub-optimal functions must play a pivotal role in stem cells. As such, mitophagy, as an essential mitochondrial quality control mechanism, is beginning to gain appreciation within the stem cell field. Here we review and discuss recent advances in our knowledge pertaining to the roles of mitophagy in stem cell functions and the potential contributions of this specific quality control process on to the progression of aging and diseases.

Highlights

  • Mitochondria are essential organelles within the cell responsible for a number of diverse functions including, energy metabolism, reactive oxygen species (ROS), Ca2+ dynamics, iron-sulphur cluster biogenesis and apoptosis

  • The same study reported that knockdown of BNIP3L/NIX and FUN14 Domain Containing 1 (FUNDC1) had no impact on progenitor cell fate determination or reprogramming [106], which contrasts with the above mentioned results suggesting an important role of NIX in induced pluripotent stem cells (iPSCs) reprogramming from MEFs [100]

  • Evidence for defective degradation of mitochondria has been observed in mice with inefficient degradation of engulfed mitochondria described in primary mouse neurons [123]. Further to this PTEN-induced kinase 1 (PINK1) has been described as downregulated in oligodendrocytes and neurons of the caudate from HD patients [124,125]. This demonstrates that mitophagy could play a role in the differentiated tissue effected by HD, this added to the changes in early neurogenesis which have been described in PD and Alzheimer’s could suggest a role for mitophagy in these stem cells which could possibly be an avenue for further study in HD

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Summary

Introduction

Mitochondria are essential organelles within the cell responsible for a number of diverse functions including, energy metabolism, reactive oxygen species (ROS), Ca2+ dynamics, iron-sulphur cluster biogenesis and apoptosis. Given the involvement of mitochondria in such fundamental cellular pathways it is imperative that these organelles are maintained in an optimal state. Biology 2020, 9, 481 several quality control mechanisms to ensure the existence of functional mitochondria. Mitochondrial quality control (MQC) is an important process that encompasses three main pathways: the mitochondrial protease and chaperone system, the mitochondrial derived vesicle (MDV) pathway and mitophagy. Mitophagy has emerged as an important mechanism in situations of mitochondrial dysfunction and during stress conditions, and during physiological conditions of development and tissue regeneration. In this review we discuss recent developments highlighting novel roles for mitophagy in stem cells and how alterations in this pathway may be involved in stem cell dysfunctions during aging and disease states

Mitophagy
Important Players in Mitophagy
Overlap and Cross Talk between Mitophagy Pathways
Mitochondria and Stem Cells
Mitochondrial Properties Associated with Stemness
Mitochondrial Phenotype Shifts Associated with Commitment and Differentiation
Mitophagy in Stem Cells
Mitophagy and iPSC Reprogramming
Mitophagy in Stem Cell Maintenance
Mitophagy in Stem Cell Differentiation
Mitophagy in Disease and Treatment
Mitophagy in Neural Stem Cell Depletion and Impaired Neurogenesis
Mitophagy in Bone Marrow Mesenchymal Stem Cells and Bone Diseases
Mitophagy in Ageing
Therapeutic Interventions
Conclusions
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