scholarly journals Deletion of Dnm1 Gene In Mitochondria Lead To The Changes of Cell Dynamics and Energy Metabolism In Fission Yeast

2021 ◽  
Author(s):  
Xiumei Tan ◽  
Xiang Ding ◽  
Rongmei Yuan ◽  
Yiling Hou
Keyword(s):  
Energy Metabolism ◽  
Schizosaccharomyces Pombe ◽  
Gene Deletion ◽  
Mitochondrial Fission ◽  
Growth Time ◽  
Growth Speed ◽  
Cell Dynamics ◽  
Atp Production ◽  
Living Cell Imaging ◽  
Intermediate Metabolite

Abstract Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The major mitochondrial fission protein is dynamin-related Drp1 GTPase (Dnm1 in yeast). The effects of Dnm1 gene deletion on cell dynamics and energy metabolism during mitosis were studied in Schizosaccharomyces pombe. Dnm1 gene deletion can lead to slow growth, abnormal sporulation, abnormal number and length of interphase microtubules of Schizosaccharomyces pombe. The deletion of Dnm1 gene can also affect the spindle growth speed and growth time of metaphase and anaphase, and affect the spindle fluorescence intensity of prophase and metaphase. At the same time, the structure and dynamics of the spindle microtubules of Dnm1Δ are also different. The statistics of spindle length showed that there was delayed spindle fracture in Dnm1Δ Cells. Two different chromosome behaviors, normal and lagged, were observed by living cell imaging. The analysis of coenzymes, intermediates and energy in energy metabolism showed that there were some abnormalities after Dnm1 gene deletion, including coenzyme defects, intermediate metabolite defects and ATP production defects.

Evolutionary Consequences of Tradeoffs between Yield and Rate of ATP Production

2002 ◽  
Vol 216 (1) ◽  
Author(s):  
Thomas Pfeiffer ◽  
Sebastian Bonhoeffer
Keyword(s):  
Game Theory ◽  
Population Dynamics ◽  
Energy Metabolism ◽  
Adenosine Triphosphate ◽  
Organic Material ◽  
High Yield ◽  
Atp Production ◽  
Cellular Processes ◽  
Quantitative Properties ◽  
Evolutionary Consequences

Adenosine triphosphate (ATP) is a key compound in the energy metabolism of cells and is required to drive vital biochemical reactions. In heterotrophic organisms ATP production is coupled to the degradation of energy-rich organic material taken up from the environment. In the transfer of the environmental energy to cellular processes heterotrophs face a tradeoff, since the conversion of the environmental energy into ATP cannot be both maximally fast and efficient. Here we show how tradeoffs between rate and yield of ATP production arise firstly from thermodynamical principles, and secondly for the ATP production by respiration and fermentation. Using methods derived from game theory and population dynamics we investigate the evolutionary consequences for both tradeoffs. We show that spatially structured environments enable the evolution of efficient pathways with high yield. The strategies of ATP production realized in a population, however, depend on the quantitative properties of the tradeoffs.

Metformin Collaborates With PINK1/Mfn2 Overexpression Prevented Isoproterenol-Induced Cardiomyocyte Injury By Improving Mitochondrial Function

2021 ◽  
Author(s):  
Zhuang Ma ◽  
Zuheng Liu ◽  
Yuting Xue ◽  
Hao Zhang ◽  
Wenjun Xiong ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Energy Metabolism ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Membrane ◽  
Mitochondrial Morphology ◽  
Dependent Manner ◽  
Combination Strategy ◽  
Mitochondrial Energy Metabolism ◽  
Atp Production

Abstract Background: Both mitochondrial quality control and energy metabolism are critical in maintaining the physiological function of cardiomyocytes. Previous studies indicated that PGC-1α is a transcription co-activator in promoting mitochondrial energy metabolism which would be beneficial for cardiomyocytes. However, PGC-1α overexpression in heart tissues could also result in the development of cardiomyopathy. This discrepancy in vivo and in vitro might be due to neglecting the elimination of damaged mitochondrial. Thus, an integration strategy of mitochondrial biogenesis and mitophagy might be beneficial.Methods: We studied the function of PINK1 in mitophagy in isoproterenol (Iso)-induced cardiomyocyte injury. Adenovirus was used to provoke an overexpression of the PINK1/Mfn2 protein. Mitochondrial morphology was examined via electron microscopy and confocal microscopy. Cardiomyocytes injury were measured by mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and apoptosis. Metformin was used to increase mitochondrial biogenesis, the level of which was detected via immunoblotting. Additionally, mitochondrial respiratory function was measured by ATP production and oxygen consumption rate (OCR). Results: Cardiomyocytes treated with Iso had high levels of PINK1 and low levels of Mfn2 in a time-dependent manner. PINK1 overexpression promoted mitophagy, alleviated Iso-induced reduction in MMP, reduced ROS production and the apoptotic rate. In addition to increasing mitophagy, metformin could promote mitochondrial biogenensis and the overexpression of Mfn2 induce mitochondrial fusion. Moreover, metformin treatment and PINK1/Mfn2 overexpression reduced the mitochondrial dysfunction by inhibiting the generation of ROS, and leading to an increase in both ATP production and mitochondrial membrane potential in Iso-induced cardiomyocytes injury. Conclusion: Our findings indicate that a combination strategy may help ameliorate myocardial injury through mitophagy and mitochondrial biogenesis.

scholarly journals Analysis of Activity-Dependent Energy Metabolism in Mice Reveals Regulation of Mitochondrial Fission and Fusion mRNA by Voluntary Physical Exercise in Subcutaneous Fat from Male Marathon Mice (DUhTP)

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2697
Author(s):  
Julia Brenmoehl ◽  
Daniela Ohde ◽  
Christina Walz ◽  
Martina Langhammer ◽  
Julia Schultz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Energy Metabolism ◽  
Fat Mass ◽  
Mitochondrial Fission ◽  
Subcutaneous Fat ◽  
Voluntary Exercise ◽  
Heart Weight ◽  
Mitochondrial Energy Metabolism ◽  
Voluntary Physical Activity

Physical inactivity is considered as one of the main causes of obesity in modern civilizations, and it has been demonstrated that resistance training programs can be used to reduce fat mass. The effects of voluntary exercise on energy metabolism are less clear in adipose tissue. Therefore, the effects of three different voluntary exercise programs on the control of energy metabolism in subcutaneous fat were tested in two different mouse lines. In a cross-over study design, male mice were kept for three or six weeks in the presence or absence of running wheels. For the experiment, mice with increased running capacity (DUhTP) were used and compared to controls (DUC). Body and organ weight, feed intake, and voluntary running wheel activity were recorded. In subcutaneous fat, gene expression of browning markers and mitochondrial energy metabolism were analyzed. Exercise increased heart weight in control mice (p < 0.05) but significantly decreased subcutaneous, epididymal, perinephric, and brown fat mass in both genetic groups (p < 0.05). Gene expression analysis revealed higher expression of browning markers and individual complex subunits present in the electron transport chain in subcutaneous fat of DUhTP mice compared to controls (DUC; p < 0.01), independent of physical activity. While in control mice, voluntary exercise had no effect on markers of mitochondrial fission or fusion, in DUhTP mice, reduced mitochondrial DNA, transcription factor Nrf1, fission- (Dnm1), and fusion-relevant transcripts (Mfn1 and 2) were observed in response to voluntary physical activity (p < 0.05). Our findings indicate that the superior running abilities in DUhTP mice, on one hand, are connected to elevated expression of genetic markers for browning and oxidative phosphorylation in subcutaneous fat. In subcutaneous fat from DUhTP but not in unselected control mice, we further demonstrate reduced expression of genes for mitochondrial fission and fusion in response to voluntary physical activity.

scholarly journals Porphyromonas gingivalis infection promotes mitochondrial dysfunction through Drp1-dependent mitochondrial fission in endothelial cells

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Tong Xu ◽  
Qin Dong ◽  
Yuxiao Luo ◽  
Yanqing Liu ◽  
Liang Gao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mitochondrial Dysfunction ◽  
Porphyromonas Gingivalis ◽  
Vascular Endothelial Cells ◽  
Mitochondrial Fission ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fragmentation ◽  
Atp Production ◽  
Luminescence Assay ◽  
The Impact

AbstractPorphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite mechanisms remain elusive. Emerging evidence supports an association between mitochondrial dysfunction and AS. In our study, the impact of P. gingivalis on mitochondrial dysfunction and the potential mechanism were investigated. The mitochondrial morphology of EA.hy926 cells infected with P. gingivalis was assessed by transmission electron microscopy, mitochondrial staining, and quantitative analysis of the mitochondrial network. Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP) levels. Cellular ATP production was examined by a luminescence assay kit. The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence. Mdivi-1, a specific Drp1 inhibitor, was used to elucidate the role of Drp1 in mitochondrial dysfunction. Our findings showed that P. gingivalis infection induced mitochondrial fragmentation, increased the mtROS levels, and decreased the MMP and ATP concentration in vascular endothelial cells. We observed upregulation of Drp1 (Ser616) phosphorylation and translocation of Drp1 to mitochondria. Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P. gingivalis. Collectively, these results revealed that P. gingivalis infection promoted mitochondrial fragmentation and dysfunction, which was dependent on Drp1. Mitochondrial dysfunction may represent the mechanism by which P. gingivalis exacerbates atherosclerotic lesions.

scholarly journals Energy-modulating vitamins – a new combinatorial therapy prevents cancer cachexia in rat mammary carcinoma

2005 ◽  
Vol 93 (6) ◽  
pp. 901-909 ◽  
Author(s):  
Selvanathan Saravana Perumal ◽  
Palanivelu Shanthi ◽  
Panchanadham Sachdanandam
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Oral Administration ◽  
Cancer Cells ◽  
Mammary Carcinoma ◽  
Cancer Cachexia ◽  
Krebs Cycle ◽  
Mitochondrial Enzymes ◽  
Atp Production

Mitochondria are the major intracellular organelles producing ATP molecules via the electron transport chain. Cancer cells have a deviant energy metabolism, and a high rate of glycolysis is related to a high degree of dedifferentiation and proliferation. The overall net ATP production is diminished with cancer, which ultimately leads to cancer cachexia. The present study was designed to investigate the altered energy metabolism in cancer cells and to enhance ATP production in the normal host cell metabolism by enhancing the activities of mitochondrial enzymes, using energy-modulating vitamins, and thus prevent cancer cachexia. Female Sprague–Dawley rats were selected for the experimental study. Mammary carcinoma was induced by the oral administration of 7,12-dimethylbenz[a]anthracene (25 mg/kg body weight), and treatment was started by the oral administration of the energy-modulating vitamins riboflavin (45 mg/kg body weight per d), niacin (100 mg/kg body weight per d) and coenzyme Q10(40 mg/kg body weight per d) for 28 d. Mitochondria were isolated from the mammary gland and liver of all four groups, and the Krebs cycle and oxidative phosphorylation enzymes were assayed. In mammary carcinoma-bearing animals, the activities of the Krebs cycle and oxidative phosphorylation enzymes were significantly decreased. These activities were restored to a greater extent in animals treated with energy-modulating vitamins. From these experimental results, one may hypothesize that the combination therapy of energy-modulating vitamins could be of major therapeutic value in breast cancer.

scholarly journals Methods on erg9 gene deletion in Schizosaccharomyces pombe

2009 ◽  
Vol 4 (5) ◽  
pp. 759-764
Author(s):  
Bing Cheng ◽  
Qi-peng Yuan ◽  
Xin-xiao Sun ◽  
Wen-jin Li
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Gene Deletion

scholarly journals p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells

2018 ◽  
Vol 115 (33) ◽  
pp. 8370-8375 ◽  
Author(s):  
Hidekazu Nagano ◽  
Naoko Hashimoto ◽  
Akitoshi Nakayama ◽  
Sawako Suzuki ◽  
Yui Miyabayashi ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Immunohistochemical Analysis ◽  
Cellular Functions ◽  
Atp Production ◽  
Chip Sequencing ◽  
Metastasis Models ◽  
Tumor Growth And Metastasis

The tumor suppressor p53 regulates multiple cellular functions, including energy metabolism. Metabolic deregulation is implicated in the pathogenesis of some cancers and in metabolic disorders and may result from the inactivation of p53 functions. Using RNA sequencing and ChIP sequencing of cancer cells and preadipocytes, we demonstrate that p53 modulates several metabolic processes via the transactivation of energy metabolism genes including dihydropyrimidinase-like 4 (DPYSL4). DPYSL4 is a member of the collapsin response mediator protein family, which is involved in cancer invasion and progression. Intriguingly, DPYSL4 overexpression in cancer cells and preadipocytes up-regulated ATP production and oxygen consumption, while DPYSL4 knockdown using siRNA or CRISPR/Cas9 down-regulated energy production. Furthermore, DPYSL4 was associated with mitochondrial supercomplexes, and deletion of its dihydropyrimidinase-like domain abolished its association and its ability to stimulate ATP production and suppress the cancer cell invasion. Mouse-xenograft and lung-metastasis models indicated that DPYSL4 expression compromised tumor growth and metastasis in vivo. Consistently, database analyses demonstrated that low DPYSL4 expression was significantly associated with poor survival of breast and ovarian cancers in accordance with its reduced expression in certain types of cancer tissues. Moreover, immunohistochemical analysis using the adipose tissue of obese patients revealed that DPYSL4 expression was positively correlated with INFg and body mass index in accordance with p53 activation. Together, these results suggest that DPYSL4 plays a key role in the tumor-suppressor function of p53 by regulating oxidative phosphorylation and the cellular energy supply via its association with mitochondrial supercomplexes, possibly linking to the pathophysiology of both cancer and obesity.

scholarly journals Function and Mechanism of Trimetazidine in Myocardial Infarction-Induced Myocardial Energy Metabolism Disorder Through the SIRT1–AMPK Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiu-ying Luo ◽  
Ze Zhong ◽  
Ai-guo Chong ◽  
Wei-wei Zhang ◽  
Xin-dong Wu
Keyword(s):  
Myocardial Infarction ◽  
Energy Metabolism ◽  
Ischemia Reperfusion ◽  
Heart Weight ◽  
Coronary Artery Ligation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Myocardial Energy Metabolism ◽  
Atp Production ◽  
Ampk Pathway

Myocardial energy metabolism (MEM) is an important factor of myocardial injury. Trimetazidine (TMZ) provides protection against myocardial ischemia/reperfusion injury. The current study set out to evaluate the effect and mechanism of TMZ on MEM disorder induced by myocardial infarction (MI). Firstly, a MI mouse model was established by coronary artery ligation, which was then treated with different concentrations of TMZ (5, 10, and 20 mg kg–1 day–1). The results suggested that TMZ reduced the heart/weight ratio in a concentration-dependent manner. TMZ also reduced the levels of Bax and cleaved caspase-3 and promoted Bcl-2 expression. In addition, TMZ augmented adenosine triphosphate (ATP) production and superoxide dismutase (SOD) activity induced by MI and decreased the levels of lipid peroxide (LPO), free fatty acids (FFA), and nitric oxide (NO) in a concentration-dependent manner (all P &lt; 0.05). Furthermore, an H2O2-induced cell injury model was established and treated with different concentrations of TMZ (1, 5, and 10 μM). The results showed that SIRT1 overexpression promoted ATP production and reactive oxygen species (ROS) activity and reduced the levels of LPO, FFA, and NO in H9C2 cardiomyocytes treated with H2O2 and TMZ. Silencing SIRT1 suppressed ATP production and ROS activity and increased the levels of LPO, FFA, and NO (all P &lt; 0.05). TMZ activated the SIRT1–AMPK pathway by increasing SIRT1 expression and AMPK phosphorylation. In conclusion, TMZ inhibited MI-induced myocardial apoptosis and MEM disorder by activating the SIRT1–AMPK pathway.

scholarly journals Repeated hypoglycemia blunts the responsiveness of glucose-inhibited GHRH neurons by remodeling neural inputs and disrupting mitochondrial structure and function

2019 ◽  
Author(s):  
M Bayne ◽  
A Alvarsson ◽  
K Devarakonda ◽  
R Li ◽  
M Jimenez-Gonzalez ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Glucose Deprivation ◽  
Glucose Sensing ◽  
Diabetic Patients ◽  
Hypoglycemia Unawareness ◽  
Atp Production ◽  
Low Glucose

AbstractHypoglycemia is a frequent complication of diabetes, limiting therapy and increasing morbidity and mortality. With recurrent hypoglycemia, the counter-regulatory response (CRR) to decreased blood glucose is blunted, resulting in hypoglycemia unawareness. The mechanisms leading to these blunted effects remain incompletely understood. Here, we identify, with in situ hybridization, immunohistochemistry and the tissue clearing capability of iDisco, that GHRH neurons represent a unique population of arcuate nucleus neurons activated by glucose deprivation in vivo. Repeated glucose deprivation reduces GHRH neuron activation and remodels excitatory and inhibitory inputs to GHRH neurons. We show low glucose sensing is coupled to GHRH neuron depolarization, decreased ATP production and mitochondrial fusion. Repeated hypoglycemia attenuates these responses during low glucose. By maintaining mitochondrial length with the small molecule, mdivi-1, we preserved hypoglycemia sensitivity in vitro and in vivo. Our findings present possible mechanisms for the blunting of the CRR, broaden significantly our understanding of the structure of GHRH neurons and for the fist time, propose that mitochondrial dynamics play an important role in hypoglycemia unawareness. We conclude that interventions targeting mitochondrial fission in GHRH neurons may offer a new pathway to prevent hypoglycemia unawareness in diabetic patients.

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