Mitophagy: A New Player in Stem Cell Biology

Abstract

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.

Towards Tissue-Specific Stem Cell Therapy for the Intervertebral Disc: PPARδ Agonist Increases the Yield of Human Nucleus Pulposus Progenitor Cells in Expansion

“…On the contrary, this "self-renewal path of PPARδ agonist mitophagy" could not be demonstrated for hematopoietic Tie2-stem cells [20]. Furthermore, mitophagy induces stem cell behavior by a complex regulation of metabolism, calcium, and reactive oxygen species (ROS) [22].…”

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

“…In addition, emerging evidence suggests that mitophagy may regulate both stemness and differentiation of stem cells, possibly in a tissue-specific manner [ 104 ]. Indeed, given that mitochondria have essential roles throughout neurogenesis, it is likely that mitophagy—a subclass of autophagy that selectively degrades damaged mitochondria—is also important in this process.…”

New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy

“…One example of this targeted approach, termed mitophagy, is the engulfment of predominantly defunct/dysfunctional mitochondria [43]. This process, alongside mitochondrial biogenesis (discussed later), is seen as essential to maintain a healthy and functioning cell, not only maintaining homeostasis in fully differentiated tissues basally but also playing a role in the differentiation process of different tissues as well as the adaption of tissues in response to different cellular stress [44,45]. Broadly speaking, mitophagy uses many of the same mechanisms observed in general autophagy but utilises certain proposed strategies to guide the autophagosome formation around the mitochondria, targeted for destruction [45,46].…”

“…The most well studied of these is the PTENinduced kinase 1 (PINK1) and PARKIN mechanism for mitochondrial targeting. Briefly, whilst the mitochondria fully functioning PINK1 is translocated across the outer and then inner mitochondrial membranes before being cleaved by the protease preselin-associated rhomboid-like (PARL) [44,45,47,48]. The two subsequent fragments are then degraded, one in the mitochondria and the other translocates back out of the mitochondria and degraded in the cytoplasm, with this process happening in a constant and rapid fashion [45,[47][48][49][50].…”