Proteomic profiling reveals mitochondrial alterations in Rett syndrome

Cicaloni, Vittoria; Pecorelli, Alessandra; Tinti, Laura; Rossi, Marco; Benedusi, Mascia; Cervellati, Carlo; Spiga, Ottavia; Santucci, Annalisa; Hayek, Joussef; Salvini, Laura; Tinti, Cristina; Valacchi, Giuseppe

doi:10.1016/j.freeradbiomed.2020.05.014

Cited by 22 publications

(22 citation statements)

References 67 publications

(161 reference statements)

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“…Our study explored, for the first time, the Mitophagy plays pivotal roles in the maintenance of mitochondrial homeostasis. Dysregulation of mitophagy has been found to be involved in the pathogenesis of a wide variety of diseases, such as Alzheimer's disease (Han et al, 2020), Rett syndrome (Cicaloni et al, 2020), polycystic ovary syndrome (Yi et al, 2020) and DN (Saxena et al, 2019). In HG-stimulated renal tubular cells, the mitochondrial dysfunction leads to excessive ROS release (Wei & Szeto, 2019 In the present study, we found a decreased level of miR-150-5p in response to HG, which exacerbated HG-mediated HK-2 cell injury by reducing mitophagy.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR‐150‐5p–DRP1 axis in diabetic nephropathy

Yang

Zhou

Liu

et al. 2021

Experimental Physiology

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Diabetic nephropathy (DN) is a severe complication in diabetic patients, with a high mortality rate. Renal tubular injury is involved in the pathogenesis of DN. In this study, we aimed to uncover the regulatory roles of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and its possible mechanisms. High glucose-challenged HK-2 cells were used as an in vitro DN model. NEAT1, miR-150-5p and DRP1 levels were assessed by RT-qPCR. Cell viability was determined by the MTT assay. MitoSOX Red and JC-1 were used to evaluate intracellular production of reactive oxygen species and mitochondrial membrane potential, respectively. Lactate dehydrogenase release and superoxide dismutase activity were assessed with commercial kits. The protein levels of DRP1, p62, BECN1(beclin 1) and BNIP3 were determined by western blotting. The interaction between NEAT1 (DRP1) and miR-150-5p was verified by a dual-luciferase reporter assay and an RNA immunoprecipitation assay. Our results showed that in response to high glucose the NEAT1 and DRP1 levels were upregulated, whereas the miR-150-5p level was downregulated in HK-2 cells. Knockdown of NEAT1 or DRP1 in high glucose-challenged HK-2 cells inhibited excessive reactive oxygen species production and lactate dehydrogenase release, increased cell viability, mitochondrial membrane potential and superoxide dismutase activity and enhanced mitophagy. Inhibition of miR-150-5p resulted in the opposite results. Mechanistically, NEAT1 sponged miR-150-5p to increase the DRP1 level. Moreover, silencing of NEAT1 or DRP1 could counteract miR-150-5p inhibition-induced deleterious effects. Collectively, our findings indicate that NEAT1 facilitates high glucose-induced damage in HK-2 cells by suppressing mitophagy via the miR-150-5p-DRP 1 axis, which sheds light on a novel mechanism of DN.

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Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR‐150‐5p–DRP1 axis in diabetic nephropathy

Yang

Zhou

Liu

et al. 2021

Experimental Physiology

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“…Although there are still many unresolved questions in RTT neuropathology, previous studies have suggested pathogenic elements, including biogenic amines and mitochondrial functions [83,84]. Dopamine is a biogenic amine associated with involuntary movements and autonomic dysfunction in RTT symptoms.…”

Section: Rett Syndromementioning

confidence: 99%

“…Dopamine is a biogenic amine associated with involuntary movements and autonomic dysfunction in RTT symptoms. Patients and MeCP2-deficient models in RTT have shown altered expression of many genes encoding proteins that control mitochondrial morphology and function [84,85]. Further, biogenic amines and mitochondria have also been proposed as potential therapeutic targets for RTT [83,84].…”

Section: Rett Syndromementioning

confidence: 99%

Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

Masuda

Han

Kato

et al. 2021

IJMS

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A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.

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“…Rett syndrome (which has been studied much more than PPM-X syndrome) has many characteristics in common with mitochondrial disorders, ranging from delayed development and muscle weakness to seizures and heart problems [93,94]. Either directly or indirectly, the MECP2 gene affects the expression of nuclear genes that regulate mitochondrial functions [94].…”

Section: Mitochondria In the MIXmentioning

confidence: 99%

“…Either directly or indirectly, the MECP2 gene affects the expression of nuclear genes that regulate mitochondrial functions [94]. And cells of Rett-syndrome patients, just like healthy rodent cells from which the MECP2 gene has been knocked out, contain malformed, poorly functioning mitochondria that produce little energy and a lot of free radicals [93,94]. Anti-inflammatory dietary supplements that neutralize free radicals, such as fish oil, improve Rett symptoms in girls, suggesting that mitochondrial dysfunction contributes to the syndrome rather than being a mere side effect of it [95].…”

Section: Mitochondria In the MIXmentioning

confidence: 99%

Mental health, mitochondria, and the battle of the sexes

Bressan¹,

Krämer²

2021

Preprint

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This paper presents a broad perspective on how mental disease relates to the different evolutionary strategies of men and women and to growth, metabolism, and mitochondria—the enslaved bacteria in our cells that enable it all. Several mental disorders strike one sex more than the other; yet what truly matters, regardless of one’s sex, is how much one’s brain is “female” and how much it is “male”. This appears to be the result of an arms race between the parents over how many resources their child ought to extract from the mother, hence whether it should grow a lot or stay small and undemanding. An uneven battle alters the child’s risk of developing not only insulin resistance, diabetes, or cancer, but a mental disease as well. Maternal supremacy increases the odds of a psychosis-spectrum disorder; paternal supremacy, those of an autism-spectrum one. And a particularly lopsided struggle may invite one or the other of a series of syndromes that come in pairs, with diametrically opposite, excessively “male” or “female” characteristics. By providing the means for this tug of war, mitochondria take center stage in steadying or upsetting the precarious balance on which our mental health is built.

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Proteomic profiling reveals mitochondrial alterations in Rett syndrome

Cited by 22 publications

References 67 publications

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR‐150‐5p–DRP1 axis in diabetic nephropathy

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR‐150‐5p–DRP1 axis in diabetic nephropathy

Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

Mental health, mitochondria, and the battle of the sexes

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