scholarly journals Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics

2015 ◽  
Vol 112 (45) ◽  
pp. 13910-13915 ◽  
Author(s):  
Laura Pancrazi ◽  
Giulietta Di Benedetto ◽  
Laura Colombaioni ◽  
Grazia Della Sala ◽  
Giovanna Testa ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Differentiation ◽  
Mitochondrial Fission ◽  
Cellular Functions ◽  
Forebrain Development ◽  
Forkhead Box ◽  
Pathological Conditions ◽  
Mouse Cortex ◽  
Mitochondrial Functions ◽  
Glial Cell Cultures

Forkhead box g1 (Foxg1) is a nuclear-cytosolic transcription factor essential for the forebrain development and involved in neurodevelopmental and cancer pathologies. Despite the importance of this protein, little is known about the modalities by which it exerts such a large number of cellular functions. Here we show that a fraction of Foxg1 is localized within the mitochondria in cell lines, primary neuronal or glial cell cultures, and in the mouse cortex. Import of Foxg1 in isolated mitochondria appears to be membrane potential-dependent. Amino acids (aa) 277–302 were identified as critical for mitochondrial localization. Overexpression of full-length Foxg1 enhanced mitochondrial membrane potential (ΔΨm) and promoted mitochondrial fission and mitosis. Conversely, overexpression of the C-term Foxg1 (aa 272–481), which is selectively localized in the mitochondrial matrix, enhanced organelle fusion and promoted the early phase of neuronal differentiation. These findings suggest that the different subcellular localizations of Foxg1 control the machinery that brings about cell differentiation, replication, and bioenergetics, possibly linking mitochondrial functions to embryonic development and pathological conditions.

scholarly journals FOXC1 in cancer development and therapy: deciphering its emerging and divergent roles

2017 ◽  
Vol 9 (12) ◽  
pp. 797-816 ◽  
Author(s):  
Zhi Yang ◽  
Shuai Jiang ◽  
Yicheng Cheng ◽  
Tian Li ◽  
Wei Hu ◽  
...  
Keyword(s):  
Transcriptional Regulator ◽  
Cancer Development ◽  
Protein Activity ◽  
Stem Cell Maintenance ◽  
Cancer Migration ◽  
Forkhead Box ◽  
Pathological Conditions ◽  
Clinical Biomarker ◽  
Abnormal Cell Proliferation ◽  
Cell Maintenance

Forkhead box C1 (FOXC1) is an essential member of the forkhead box transcription factors and has been highlighted as an important transcriptional regulator of crucial proteins associated with a wide variety of carcinomas. FOXC1 regulates tumor-associated genes and is regulated by multiple pathways that control its mRNA expression and protein activity. Aberrant FOXC1 expression is involved in diverse tumorigenic processes, such as abnormal cell proliferation, cancer stem cell maintenance, cancer migration, and angiogenesis. Herein, we review the correlation between the expression of FOXC1 and tumor behaviors. We also summarize the mechanisms of the regulation of FOXC1 expression and activity in physiological and pathological conditions. In particular, we focus on the pathological processes of cancer targeted by FOXC1 and discuss whether FOXC1 is good or detrimental during tumor progression. Moreover, FOXC1 is highlighted as a clinical biomarker for diagnosis or prognosis in various human cancers. The information reviewed here should assist in experimental designs and emphasize the potential of FOXC1 as a therapeutic target for cancer.

scholarly journals The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 489
Author(s):  
Hilary Y. Liu ◽  
Jenna R. Gale ◽  
Ian J. Reynolds ◽  
John H. Weiss ◽  
Elias Aizenman
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Neuronal Damage ◽  
Mitochondrial Fission ◽  
Permeability Transition ◽  
High Energy ◽  
Atp Depletion ◽  
Ros Generation ◽  
Cellular Functions ◽  
Calcium Deregulation ◽  
Energy Demands

Zinc is a highly abundant cation in the brain, essential for cellular functions, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential (MMP), leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and excitotoxic calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting.

scholarly journals SIRT4 regulates rat dental papilla cell differentiation by promoting mitochondrial functions

2021 ◽  
Vol 134 ◽  
pp. 105962
Author(s):  
Haoling Chen ◽  
Jun Kang ◽  
Fuping Zhang ◽  
Tong Yan ◽  
Wenguo Fan ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Dental Papilla ◽  
Mitochondrial Functions

scholarly journals The study on optogenetic tachyarrhythmia termination under pathological conditions from the single cell to the whole heart

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Ordog ◽  
E.C.A Nyns ◽  
M.S Fontes ◽  
T Van Den Heuvel ◽  
C.I Bart ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Gene Delivery ◽  
The Netherlands ◽  
Cardiac Disease ◽  
Neonatal Rat ◽  
Funding Source ◽  
In Vivo Models ◽  
Pathological Conditions ◽  
Whole Heart

Abstract Background Ventricular tachyarrhytmias (VTs) are common among patients suffering from cardiac remodeling and cause significant morbidity and mortality. Current research and treatment options for such VTs are suboptimal, hence new strategies are urgently needed. Optogenetics offers efficacious means to control cardiac rhythm, including shock-free VT termination. However, this has not been demonstrated in diseased hearts in vivo, while clinical translation would not only require such demonstration, but also an in-depth understanding of cellular responses. Purpose To assess the optogenetic response at the cardiac cell, tissue, and whole heart level in terms of rhtyhm control under pathological conditions by an integrative experimental platform including in vitro and in vivo models of cardiac disease. Methods Remodeling was induced in neonatal rat ventricular cardiomyocytes (NRVMs) by phenylephrine (PE) exposure. Pathological conditions leading to ventricular remodeling were mimicked by transverse aortic constriction (TAC) surgery in adult rats. The light-activated ion channel ReaChR was ectopically expressed in NRVMs and in hearts of TAC and sham animals by viral vector-based gene delivery. Results Electrical and structural remodeling was evidenced by elongated action potential durations (p<0.05) and increased cell capacitance (p<0.05) in PE-treated, but not in control cells (CTL). Light-induced ionic currents in ReaChR-expressing PE-treated and CTL NRVMs displayed comparable kinetic properties and current densities (p>0.05). Illumination (1 s) caused a sudden shift in membrane potential leading to a plateau at −7.3 mV for PE-treated and −18.9 mV for CTL cells (p>0.05). Hearts explanted from TAC animals showed increased average heart weight to body weight ratio, ventricular fibrosis and expression of hypertrophy markers (ANP, aSkMA, p<0.05), while tissue preparations showed significant APD increase compared to sham. In vivo gene delivery resulted in expression of the ReaChR-citrine transgene in ∼80% of isolated ventricular myocytes (VMs). Photocurrent densities were not different (p>0.05) in VMs from TAC and sham animals, which currents led to comparable shifts in membrane potential (65.3 mV for TAC and 63.9 mV for CTL). In line with this, illumination caused marked depolarization in tissue preparations (from −77.6 to −16.4 mV) in TAC animals as assessed by conventional sharp electrode measurements. Importantly, as anticipated, electrically-induced VT episodes could be terminated in open chest experiments in TAC animals (n=6; 76.3% of cases) by epicardial illumination in vivo. Conclusions Key operational parameters of the optogenetic response remained unaffected in models of cardiac disease, which allowed efficacious optogenetic VT termination in the diseased rat heart exhibiting structural and electrical remodeling. These findings corroborate the translational potential of shock-free therapy of cardiac arrhythmia by optogenetics. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This work was supported by personal funding from the Netherlands Organization for Scientific Research (NWO, Vidi grant 1714336 to D.A.P.). D.A.P. is also a recipient of the European Research Council (ERC), Starting grant (716509). Additional support was provided by the Netherlands Heart Institute (ICIN grant 230.148-04 to A.A.F.d.V.).

Impaired Mitochondrial functions and Energy Metabolism in MPTP-induced Model of Parkinson’s Disease in Mice: Comparison of Strains and Dose Regimens

2021 ◽  
Author(s):  
Anjana Pathania ◽  
Priyanka Garg ◽  
Rajat Sandhir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Membrane Potential ◽  
Metabolic Pathways ◽  
Citrate Synthase ◽  
Mitochondrial Respiratory Chain ◽  
Progression Rate ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Mptp Treatment

Abstract Parkinson’s disease is a multiplexed disease involving diverse symptoms and progression rate. Heterogenous diseases need an efficient animal model to enhance the understanding of the underlying mechanism. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin, has been widely used to replicate the pathophysiology of PD in rodents, but its effect on energy metabolic perturbation is limited. Moreover, susceptibility to different dosage regime of MPTP varies among mice strains. Thus, herein the present study compares the effect of acute and sub-acute MPTP dosage regimes on mitochondrial functions in terms of mitochondrial respiratory chain enzymes, mitochondrial swelling and membrane potential in C57BL/6 and Balb/c mice. In addition, activities of enzymes involved in energy metabolic pathways were also studied along with behaviour and neurochemical alterations. The results showed that acute dose of MPTP in C57BL/6 mice had more profound effect on the enzyme activities of electron transport chain complexes. Further, the activity of MAO-A and MAO-B was increased following acute and sub-acute MPTP administration in C57BL/6 mice. However, no significant change was observed in Balb/c strain. Acute MPTP treatment resulted in decreased mitochondrial membrane potential along with swelling of mitochondria in C57BL/6 mice. In addition, perturbations were observed in hexokinase and pyruvate dehydrogenase of glycolysis pathway and citrate synthase, aconitase, isocitrate dehydrogenase and fumarase of TCA cycle. Moreover, acute MPTP led to pronounced depletion in neostriatal dopamine levels in C57BL/6 than in Balb/c mice. Behavioral tests such as open field, Narrow beam walk test and footprint test showed that locomotor activity was drastically reduced as an acute effect of MPTP in C57BL/6 mice strain. Therefore, these results consistently showed that acute MPTP treatment in C57BL/6 strain had severe mitochondrial dysfunctions, perturbed energy metabolic pathways, altered neurotransmission and motor defects as compared to Balb/c strain. Thus, the findings suggest that the dose and strain of mice need to consider for pre-clinical studies targeting mitochondrial dysfunctions in MPTP-induced Parkinson’s disease model.

scholarly journals The Translocator Protein (TSPO) in Mitochondrial Bioenergetics and Immune Processes

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 512 ◽  
Author(s):  
Calina Betlazar ◽  
Ryan J. Middleton ◽  
Richard Banati ◽  
Guo-Jun Liu
Keyword(s):  
Paradigm Shift ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Translocator Protein ◽  
Imaging Studies ◽  
Immunomodulatory Effects ◽  
Cellular Functions ◽  
Mitochondrial Functions ◽  
Cellular Bioenergetics ◽  
Mitochondrial Membrane Protein

The translocator protein (TSPO) is an outer mitochondrial membrane protein that is widely used as a biomarker of neuroinflammation, being markedly upregulated in activated microglia in a range of brain pathologies. Despite its extensive use as a target in molecular imaging studies, the exact cellular functions of this protein remain in question. The long-held view that TSPO plays a fundamental role in the translocation of cholesterol through the mitochondrial membranes, and thus, steroidogenesis, has been disputed by several groups with the advent of TSPO knockout mouse models. Instead, much evidence is emerging that TSPO plays a fundamental role in cellular bioenergetics and associated mitochondrial functions, also part of a greater role in the innate immune processes of microglia. In this review, we examine the more direct experimental literature surrounding the immunomodulatory effects of TSPO. We also review studies which highlight a more central role for TSPO in mitochondrial processes, from energy metabolism, to the propagation of inflammatory responses through reactive oxygen species (ROS) modulation. In this way, we highlight a paradigm shift in approaches to TSPO functioning.

scholarly journals Flow-cytometric study of vital cellular functions in Escherichia coli during solar disinfection (SODIS)

Microbiology ◽  
2006 ◽  
Vol 152 (6) ◽  
pp. 1719-1729 ◽  
Author(s):  
Michael Berney ◽  
Hans-Ulrich Weilenmann ◽  
Thomas Egli
Keyword(s):  
Escherichia Coli ◽  
Membrane Potential ◽  
Glucose Uptake ◽  
Efflux Pump ◽  
Cellular Functions ◽  
Solar Disinfection ◽  
E Coli ◽  
Pump Activity ◽  
Uva Light ◽  
Uptake Activity

The effectiveness of solar disinfection (SODIS), a low-cost household water treatment method for developing countries, was investigated with flow cytometry and viability stains for the enteric bacterium Escherichia coli. A better understanding of the process of injury or death of E. coli during SODIS could be gained by investigating six different cellular functions, namely: efflux pump activity (Syto 9 plus ethidium bromide), membrane potential [bis-(1,3-dibutylbarbituric acid)trimethine oxonol; DiBAC4(3)], membrane integrity (LIVE/DEAD BacLight), glucose uptake activity (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose; 2-NBDG), total ATP concentration (BacTiter-Glo) and culturability (pour-plate method). These variables were measured in E. coli K-12 MG1655 cells that were exposed to either sunlight or artificial UVA light. The inactivation pattern of cellular functions was very similar for both light sources. A UVA light dose (fluence) of <500 kJ m−2 was enough to lower the proton motive force, such that efflux pump activity and ATP synthesis decreased significantly. The loss of membrane potential, glucose uptake activity and culturability of >80 % of the cells was observed at a fluence of ∼1500 kJ m−2, and the cytoplasmic membrane of bacterial cells became permeable at a fluence of >2500 kJ m−2. Culturable counts of stressed bacteria after anaerobic incubation on sodium pyruvate-supplemented tryptic soy agar closely correlated with the loss of membrane potential. The results strongly suggest that cells exposed to >1500 kJ m−2 solar UVA (corresponding to 530 W m−2 global sunlight intensity for 6 h) were no longer able to repair the damage and recover. Our study confirms the lethal effect of SODIS with cultivation-independent methods and gives a detailed picture of the ‘agony’ of E. coli when it is stressed with sunlight.

Alterations in glycosylation as biomarkers for cancer detection

2010 ◽  
Vol 63 (4) ◽  
pp. 322-329 ◽  
Author(s):  
Celso A Reis ◽  
Hugo Osorio ◽  
Luisa Silva ◽  
Catarina Gomes ◽  
Leonor David
Keyword(s):  
Cell Differentiation ◽  
Cancer Detection ◽  
Human Cancer ◽  
Protein Glycosylation ◽  
Cell Trafficking ◽  
Tumour Invasion ◽  
Host Pathogen Interactions ◽  
Pathological Conditions ◽  
Major Class ◽  
Host Pathogen

Glycoconjugates constitute a major class of biomolecules which include glycoproteins, glycosphingolipids and proteoglycans. Glycans are involved in several physiological and pathological conditions, such as host–pathogen interactions, cell differentiation, migration, tumour invasion and metastisation, cell trafficking and signalling. Cancer is associated with glycosylation alterations in glycoproteins and glycolipids. This review describes various aspects of protein glycosylation with the focus on alterations associated with human cancer. The application of these glycosylation modifications as biomarkers for cancer detection in tumour tissues and serological assays is summarised.

scholarly journals Acupuncture May Exert Its Therapeutic Effect through MicroRNA-339/Sirt2/NFκB/FOXO1 Axis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jia-You Wang ◽  
Hui Li ◽  
Chun-Mei Ma ◽  
Jia-Lu Wang ◽  
Xin-Sheng Lai ◽  
...  
Keyword(s):  
Acupuncture Therapy ◽  
Critical Role ◽  
Luciferase Assay ◽  
Cellular Functions ◽  
Physiological Level ◽  
Forkhead Box ◽  
Bioinformatics Study ◽  
Direct Target ◽  
Future Work

Recently, we have found that a number of microRNAs (miRNAs) and proteins are involved in the response to acupuncture therapy in hypertensive rats. Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2). In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons. In human SH-SY5Y cells, the luciferase assay implied that Sirt2 was likely a target of miRNA-339. Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells. In addition, overexpression of miR-399 increased the acetylation of nuclear factor-κB (NF-κB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2. Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons. Since Sirt2 plays a critical role in multiple important cellular functions, our data imply that acupuncture may act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2/NF-κB/FOXO1 axis. Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-κB/FOXO1 axis in response to acupuncture therapy in the future work.

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