Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming

Abstract

Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity. Although we continue to gain critical insights into the mechanisms underlying mitochondrial morphology and function during cellular reprogramming – the process of reverting the fate of a differentiated cell into a stem cell, many uncertainties remain. Recent studies suggest an emerging landscape in which mitochondrial morphology and function have an active role in maintaining and regulating changes in cell identity. In this review, we will focus on these emerging concepts as crucial modulators of cellular reprogramming. Recognition of the widespread applicability of these concepts will increase our understanding of the mitochondrial mechanisms involved in cell identity, cell fate and disease.

Metabolic regulation of neurodifferentiation in the adult brain

“…In addition, the expression of two master regulators of mitochondrial biogenesis, the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and the oestrogen-related receptor gamma (ERRγ), precedes increased mitochondrial abundance [97,164]. This activation of mitochondria is marked by a remodelling and replacing the mitochondrial network [167].…”

“…Thus, the exact mechanism is not yet clear. Nevertheless, the activation of stem cells coincides with changes in mitochondrial morphology from rounded small mitochondria, with dense and compact cristae in quiescent NSCs, to a more open and structured network [167]. These changes are believed to be fundamental to neurogenesis [91,133,[171][172][173], and are possibly regulated by ROS signalling [133].…”

Role of Mitofusins and Mitophagy in Life or Death Decisions

“…The mitochondrial morphology machinery is composed by DRP1 (Dnm1 in yeast), responsible for fission, Mitofusin 1 and Mitofusin 2 (MFN1/MFN2) (Fzo1 in yeast), responsible for OM fusion and OPA1 (Mgm1 in yeast), responsible for IM fusion (Youle and van der Bliek, 2012;Tilokani et al, 2018; Figure 1A). Recent developments highlighted novel molecular determinants of mitochondrial ultrastructure dynamics (Xie et al, 2018;Kondadi et al, 2019;Rastogi et al, 2019;Snigirevskaya and Komissarchik, 2019). The fascinating plasticity of mitochondrial morphology is also brought about by post-translational modifications of the fusion and fission components, including ubiquitylation, phosphorylation, sumoylation, and proteolytic processing (Escobar-Henriques and Langer, 2014;Hofer and Wenz, 2014;Macvicar and Langer, 2016;Mishra and Chan, 2016).…”

Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells

“…We also observed that 3O-C 12 -HSL perturbed the expression of mitochondrial proteins associated with lipid metabolism and heme binding: prostaglandin E synthase 2 and cytochrome c1 heme protein ( Table 2). Indeed, fatty acid metabolism and heme binding contribute to establishment of a bioenergetically favorable environment during infection (Rastogi et al, 2019). A group of proteins became differentially abundant in response to 3O-C 12 -HSL were those with chaperone activity and involved in cell defense and response to stress: stress-70 protein, GrpE protein homolog 1, peroxiredoxin-5 (Table 2), DnaJ homolog subfamily A member 1 and thioredoxindependent peroxide reductase (Table 1).…”