Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases

Brunetti, Dario; Dykstra, Werner; Le, Stephanie; Zink, Annika; Prigione, Alessandro

doi:10.1002/stem.3425

Cited by 28 publications

(12 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eight significant modules of DEPs were visualized via the Cytoscape MCODE app ( Figure 5F ), and the mitochondria-associated oxidative phosphorylation and mitophagy were marked. The suppressive oxidative phosphorylation manifests mitochondrial impairment ( Brunetti et al, 2021 ), and mitophagy is one of the mechanisms to remove damaged mitochondria ( Shan et al, 2019 ). We found that the upregulated KEGG pathway enriched the mitophagy pathway between the Hypo + Caf and Hypo groups ( Supplementary Figure S3G ).…”

Section: Resultsmentioning

confidence: 99%

Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells

et al. 2023

View full text Add to dashboard Cite

Backgrounds: High-altitude pulmonary edema (HAPE) is a life-threatening disease without effective drugs. Caffeine is a small molecule compound with antioxidant biological activity used to treat respiratory distress syndrome. However, it is unclear whether caffeine plays a role in alleviating HAPE.Methods: We combined a series of biological experiments and label-free quantitative proteomics analysis to detect the effect of caffeine on treating HAPE and explore its mechanism in vivo and in vitro.Results: Dry and wet weight ratio and HE staining of pulmonary tissues showed that the HAPE model was constructed successfully, and caffeine relieved pulmonary edema. The proteomic results of mice lungs indicated that regulating mitochondria might be the mechanism by which caffeine reduced HAPE. We found that caffeine blocked the reduction of ATP production and oxygen consumption rate, decreased ROS accumulation, and stabilized mitochondrial membrane potential to protect AT1 cells from oxidative stress damage under hypoxia. Caffeine promoted the PINK1/parkin-dependent mitophagy and enhanced mitochondrial fission to maintain the mitochondria quality control process.Conclusion: Low-dose of caffeine alleviated HAPE by promoting PINK1/parkin-dependent mitophagy and mitochondrial fission to control the mitochondria quality. Therefore, caffeine could be a potential treatment for HAPE.

show abstract

Section: Resultsmentioning

confidence: 99%

Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The activations of both NFκB and STAT3 pathways lead to mitochondrial dysfunction [ 50 , 51 , 52 ] and increased oxidative stress [ 53 , 54 ]. It is known that mitochondrial function is critical for neurogenesis [ 55 ], with mitochondrial apoptosis and ROS levels modulating NPC proliferation [ 56 , 57 ] and differentiation [ 58 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

TNFα-Induced Oxidative Stress and Mitochondrial Dysfunction Alter Hypothalamic Neurogenesis and Promote Appetite Versus Satiety Neuropeptide Expression in Mice

et al. 2022

View full text Add to dashboard Cite

Maternal obesity results in programmed offspring hyperphagia and obesity. The increased offspring food intake is due in part to the preferential differentiation of hypothalamic neuroprogenitor cells (NPCs) to orexigenic (AgRP) vs. anorexigenic (POMC) neurons. The altered neurogenesis may involve hypothalamic bHLH (basic helix–loop–helix) neuroregulatory factors (Hes1, Mash1, and Ngn3). Whilst the underlying mechanism remains unclear, it is known that mitochondrial function is critical for neurogenesis and is impacted by proinflammatory cytokines such as TNFα. Obesity is associated with the activation of inflammation and oxidative stress pathways. In obese pregnancies, increased levels of TNFα are seen in maternal and cord blood, indicating increased fetal exposure. As TNFα influences neurogenesis and mitochondrial function, we tested the effects of TNFα and reactive oxidative species (ROS) hydrogen peroxide (H2O2) on hypothalamic NPC cultures from newborn mice. TNFα treatment impaired NPC mitochondrial function, increased ROS production and NPC proliferation, and decreased the protein expression of proneurogenic Mash1/Ngn3. Consistent with this, AgRP protein expression was increased and POMC was decreased. Notably, treatment with H2O2 produced similar effects as TNFα and also reduced the protein expression of antioxidant SIRT1. The inhibition of STAT3/NFκB prevented the effects of TNFα, suggesting that TNFα mediates its effects on NPCs via mitochondrial-induced oxidative stress that involves both signaling pathways.

show abstract

“…Speci cally, it regulates several essential cellular processes, including reactive oxygen species (ROS) signaling, calcium signaling, apoptosis, and maintaining cellular homeostasis. Recent studies demonstrate that mitochondria govern the cell fate during neurogenesis (43). Most importantly, mitochondria are the cell's powerhouse, providing energy during the differentiation of cells through oxidative phosphorylation (44).…”

Section: Discussionmentioning

confidence: 99%

KLF2 regulates neural differentiation of dental pulp-derived stem cells by modulating autophagy and mitophagy

Das

Prateeksha²,

Naidu

et al. 2022

Preprint

View full text Add to dashboard Cite

Transplantation of stem cells for treating neurodegenerative disorders is a promising future therapeutic approach. However, the molecular mechanism underlying the neuronal differentiation of mesenchymal stem cells remains inadequately explored. Therefore, the current study aims to define the regulatory role of KLF2 (Kruppel-like factor 2) during the neural differentiation (ND) of dental pulp-derived stem cells (DPSC). Herein, we showed that the expression level of KLF2, autophagy and mitophagy-associated markers were significantly elevated during ND of DPSC. We next validated our results using the chemical-mediated loss- and gain-of-function approaches. We found that the KLF2 inhibitor, GGPP (geranylgeranyl pyrophosphate) significantly reduces the ND of DPSC. Inversely, KLF2 overexpression was accomplished by using the KLF2 inducer, GGTI-298 (geranylgeranyl transferase inhibitor-298) which accelerated the molecular phenomenon of DPSC’s commitment towards ND, indicating the crucial function of KLF2 in neurogenesis. Moreover, we found that the KLF2 positively regulated autophagy, mitophagy, and the Wnt5a signaling pathway during neurogenesis. Furthermore, we measured the oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR) during ND in the presence of a KLF2 inducer or KLF2 inhibitor using the Xeflux analyzer. We found that most of the ECAR and OCR parameters were significantly increased during ND and inhibition of KLF2 marginally reversed them towards DPSC’s cellular bioenergetics. However, KLF2 overexpression shifted the cellular energy metabolism towards quiescent. Cumulatively, our findings provide the first evidence that the KLF2 critically regulates the neurogenesis of DPSC by inducing autophagy and mitophagy.

show abstract

Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases

Cited by 28 publications

References 107 publications

Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells

Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells

TNFα-Induced Oxidative Stress and Mitochondrial Dysfunction Alter Hypothalamic Neurogenesis and Promote Appetite Versus Satiety Neuropeptide Expression in Mice

KLF2 regulates neural differentiation of dental pulp-derived stem cells by modulating autophagy and mitophagy

Contact Info

Product

Resources

About