LiCl regulates mitochondrial biogenesis during megakaryocyte development

Undi, Ram Babu; Gutti, Usha; Gutti, Ravi Kumar

doi:10.1016/j.jtemb.2016.10.003

Cited by 29 publications

(17 citation statements)

References 33 publications

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“…Earlier studies showed that lithium increases PGC-1α expression and mitochondrial biogenesis in primary bovine aortic endothelial cells (Struewing et al, 2007) and megakaryocytes (Undi et al, 2017) by regulating β-catenin signalling. To understand the mechanism of CHIR-99021 on the induction of mitochondrial biogenesis, we disrupted the β-catenin signalling pathway by delivering siRNA to knock down the expression of β-catenin in hASCs.…”

Section: Discussionmentioning

confidence: 99%

CHIR-99021 regulates mitochondrial remodelling via β-catenin signalling and miRNAs during endodermal differentiation

Sun

et al. 2019

Journal of Cell Science

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Mitochondrial remodelling is a central feature of stem cell differentiation. However, little is known about the regulatory mechanisms during these processes. Previously, we found that a pharmacological inhibitor of glycogen synthase kinase-3α and-3β, CHIR-99021, initiates human adipose stem cell differentiation into human definitive endodermal progenitor cells (hEPCs), which were directed to differentiate synchronously into hepatocyte-like cells after further treatment with combinations of soluble factors. In this study, we show that CHIR-99021 promotes mitochondrial biogenesis, the expression of PGC-1α (also known as PPARGC1A), TFAM and NRF1 (also known as NFE2L1), oxidative phosphorylation capacities, and the production of reactive oxygen species in hEPCs. Blocking mitochondrial dynamics using siRNA targeting DRP1 (also known as DNM1L) impaired definitive endodermal differentiation. Downregulation of β-catenin (CTNNB1) expression weakened the effect of CHIR-99021 on the induction of mitochondrial remodelling and the expression of transcription factors for mitochondrial biogenesis. Moreover, CHIR-99021 decreased the expression of miR-19b-2-5p, miR-23a-3p, miR-23c, miR-130a-3p and miR-130a-5p in hEPCs, which target transcription factors for mitochondrial biogenesis. These data demonstrate that CHIR-99021 plays a role in mitochondrial structure and function remodelling via activation of the β-catenin signalling pathway and inhibits the expression of miRNAs during definitive endodermal differentiation. This article has an associated First Person interview with the first author of the paper.

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Section: Discussionmentioning

confidence: 99%

CHIR-99021 regulates mitochondrial remodelling via β-catenin signalling and miRNAs during endodermal differentiation

Sun

et al. 2019

Journal of Cell Science

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“…PGC-1α and mitochondrial transcription factor A (mtTFA) are often used as the markers for evaluating mitochondrial biogenesis. LiCl, a GSK-3β inhibitor, has been demonstrated to exhibit mitochondrial biogenesis by the possible mechanism that LiCl significantly up regulate the expression of PGC-1α and mtTFA with increase in DNA content in mitochondria, leading to maturation of megakaryocytes [11]. …”

Section: Gsk-3β Regulates Mitochondrial Biogenesismentioning

confidence: 99%

The Key Roles of GSK-3β in Regulating Mitochondrial Activity

Yang

Chen

Gao

et al. 2017

Cell Physiol Biochem

161

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Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been reported to show essential roles in molecular pathophysiology of many diseases. Mitochondrion is a dynamic organelle for producing cellular energy and determining cell fates. Stress-induced translocated GSK-3β may interact with mitochondrial proteins, including PI3K-Akt, PGC-1α, HK II, PKCε, components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK-3β has been implicated in mediation of mitochondrial functions. GSK-3β exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial bioenergetics, mitochondrial permeability, mitochondrial motility, and mitochondrial apoptosis. The versatile functions of GSK-3β might be associated with its wide range of substrates. Accumulative evidence demonstrates that GSK-3β inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Intensive efforts have been made for exploring GSK-3β inhibitors. Natural products provide us a great source for screening new lead compounds in inactivation of GSK-3β. The key roles of GSK-3β in mediation of mitochondrial functions are discussed in this review.

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“…Wnt/β-catenin signaling was described to stimulate biogenesis of mitochondria e.g., in C2C12 myocytes ( Yoon et al, 2010 ; Undi et al, 2017 ). As our data show that cytosolic Pgam5 activates Wnt/β-catenin signaling, we investigated whether it would also increase mitochondrial numbers.…”

Section: Resultsmentioning

confidence: 99%

“…One cellular consequence of activated Wnt/β-catenin signaling is the stimulation of mitochondrial biogenesis as shown in several cell systems ( Yoon et al, 2010 ; Undi et al, 2017 ). We propose that release of Pgam5 from damaged mitochondria represents a means of replenishing the mitochondria pool by activating Wnt/β-catenin signaling.…”

Section: Discussionmentioning

confidence: 99%