Mitochondria and the dynamic control of stem cell homeostasis

Abstract

The maintenance of cellular identity requires continuous adaptation to environmental changes. This process is particularly critical for stem cells, which need to preserve their differentiation potential over time. Among the mechanisms responsible for regulating cellular homeostatic responses, mitochondria are emerging as key players. Given their dynamic and multifaceted role in energy metabolism, redox, and calcium balance, as well as cell death, mitochondria appear at the interface between environmental cues and the control of epigenetic identity. In this review, we describe how mitochondria have been implicated in the processes of acquisition and loss of stemness, with a specific focus on pluripotency. Dissecting the biological functions of mitochondria in stem cell homeostasis and differentiation will provide essential knowledge to understand the dynamics of cell fate modulation, and to establish improved stem cell-based medical applications.

Mitochondrial plasticity in cell fate regulation

“…An important feature of maintaining mitochondrial plasticity are the ongoing fusion and fission events reshaping mitochon-drial morphology termed mitochondrial dynamics (5). Owing to their highly dynamic nature and plasticity, the mitochondria constitute an essential mediator of environmental cues with fate decisions (6). 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).…”

ZSCAN 4 + mouse embryonic stem cells have an oxidative and flexible metabolic profile

“…Stem cells need to continuously adapt to environmental changes to preserve their differentiation potential over time. Beyond energy production, it is well known that mitochondrial homeostasis plays an important role in stem cell biology at the interface between environmental cues and the control of epigenetic identity . Metabolic variations are not only an adaptation to the energy needs gradually changing according to the cellular state, but it is, instead, a cofactor determining the stem cell identity and fate through metabolites known to be active players in fundamental biological processes such as epigenetic modifications.…”

Tim29 is required for stem cell activity during regeneration in the flatworm Macrostomum lignano

“…Our findings demonstrate that healthy mitochondria are essential for proper neoblast function, and add to the increasing recognition of mitochondrial signaling as a key component to mediate stem cell activity. The emerging picture is that mitochondria continuously integrate cellular and environmental cues to influence stem cell fate and activity, which enables organisms to adapt to the environmental changes (Battersby and Richter, 2013;Lisowski et al, 2018;Zhang et al, 2018). Many questions remain, however, as the majority of published mitochondrial research focused on postmitotic tissues, and the role of mitochondria in the context of stem cells has been largely neglected until recently for several reasons (Zhang et al, 2018).…”