scholarly journals Mitochondrial Regulation by PINK1-Parkin Signaling

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Yuzuru Imai
Keyword(s):  
Quality Control ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Regulation ◽  
Upstream Regulator ◽  
Biological Studies ◽  
Mitochondrial Respiratory Chain Activity ◽  
Ubiquitin Proteasome ◽  
Respiratory Chain Activity

Two genes responsible for the juvenile Parkinson’s disease (PD), PINK1 and Parkin, have been implicated in mitochondrial quality control. The inactivation of PINK1, which encodes a mitochondrial kinase, leads to age-dependent mitochondrial degeneration in Drosophila. The phenotype is closely associated with the impairment of mitochondrial respiratory chain activity and defects in mitochondrial dynamics. Drosophila genetic studies have further revealed that PINK1 is an upstream regulator of Parkin and is involved in the mitochondrial dynamics and motility. A series of cell biological studies have given rise to a model in which the activation of PINK1 in damaged mitochondria induces the selective elimination of mitochondria in cooperation with Parkin through the ubiquitin-proteasome and autophagy machineries. Although the relevance of this pathway to PD etiology is still unclear, approaches using stem cells from patients and animal models will help to understand the significance of mitochondrial quality control by the PINK1-Parkin pathway in PD and in healthy individuals. Here I will review recent advances in our understanding of the PINK1-Parkin signaling and will discuss the roles of PINK1-Parkin signaling for mitochondrial maintenance and how the failure of this signaling leads to neurodegeneration.

scholarly journals Mitochondrial Quality Control in the Maintenance of Cardiovascular Homeostasis: The Roles and Interregulation of UPS, Mitochondrial Dynamics and Mitophagy

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yujie Song ◽  
Yuerong Xu ◽  
Yingying Liu ◽  
Jie Gao ◽  
Lele Feng ◽  
...  
Keyword(s):  
Quality Control ◽  
Mitochondrial Dynamics ◽  
Ubiquitin Proteasome System ◽  
Normal Function ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Dynamic ◽  
Profound Influence ◽  
Ubiquitin Proteasome ◽  
And Function ◽  
The Relationship

Maintenance of normal function of mitochondria is vital to the fate and health of cardiomyocytes. Mitochondrial quality control (MQC) mechanisms are essential in governing mitochondrial integrity and function. The ubiquitin-proteasome system (UPS), mitochondrial dynamics, and mitophagy are three major components of MQC. With the progress of research, our understanding of MQC mechanisms continues to deepen. Gradually, we realize that the three MQC mechanisms are not independent of each other. To the contrary, there are crosstalk among the mechanisms, which can make them interact with each other and cooperate well, forming a triangle interplay. Briefly, the UPS system can regulate the level of mitochondrial dynamic proteins and mitophagy receptors. In the process of Parkin-dependent mitophagy, the UPS is also widely activated, performing critical roles. Mitochondrial dynamics have a profound influence on mitophagy. In this review, we provide new processes of the three major MQC mechanisms in the background of cardiomyocytes and delve into the relationship between them.

scholarly journals At the heart of mitochondrial quality control: many roads to the top

2021 ◽  
Author(s):  
Roberta A. Gottlieb ◽  
Honit Piplani ◽  
Jon Sin ◽  
Savannah Sawaged ◽  
Syed M. Hamid ◽  
...  
Keyword(s):  
Quality Control ◽  
Unfolded Protein Response ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Unfolded Protein ◽  
Selective Elimination ◽  
Protein Response ◽  
Mitochondrial Unfolded Protein Response

AbstractMitochondrial quality control depends upon selective elimination of damaged mitochondria, replacement by mitochondrial biogenesis, redistribution of mitochondrial components across the network by fusion, and segregation of damaged mitochondria by fission prior to mitophagy. In this review, we focus on mitochondrial dynamics (fusion/fission), mitophagy, and other mechanisms supporting mitochondrial quality control including maintenance of mtDNA and the mitochondrial unfolded protein response, particularly in the context of the heart.

scholarly journals Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue

2021 ◽  
Vol 22 (6) ◽  
pp. 2881
Author(s):  
Clara Lefranc ◽  
Malou Friederich-Persson ◽  
Fabienne Foufelle ◽  
Aurélie Nguyen Dinh Cat ◽  
Frédéric Jaisser
Keyword(s):  
Quality Control ◽  
Adipose Tissue ◽  
Mitochondrial Dysfunction ◽  
Cellular Senescence ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Oxidative Stress ◽  
Specific Effects

Mineralocorticoid receptor (MR) expression is increased in the adipose tissue (AT) of obese patients and animals. We previously demonstrated that adipocyte-MR overexpression in mice (Adipo-MROE mice) is associated with metabolic alterations. Moreover, we showed that MR regulates mitochondrial dysfunction and cellular senescence in the visceral AT of obese db/db mice. Our hypothesis is that adipocyte-MR overactivation triggers mitochondrial dysfunction and cellular senescence, through increased mitochondrial oxidative stress (OS). Using the Adipo-MROE mice with conditional adipocyte-MR expression, we evaluated the specific effects of adipocyte-MR on global and mitochondrial OS, as well as on OS-induced damage. Mitochondrial function was assessed by high throughput respirometry. Molecular mechanisms were probed in AT focusing on mitochondrial quality control and senescence markers. Adipo-MROE mice exhibited increased mitochondrial OS and altered mitochondrial respiration, associated with reduced biogenesis and increased fission. This was associated with OS-induced DNA-damage and AT premature senescence. In conclusion, targeted adipocyte-MR overexpression leads to an imbalance in mitochondrial dynamics and regeneration, to mitochondrial dysfunction and to ageing in visceral AT. These data bring new insights into the MR-dependent AT dysfunction in obesity.

scholarly journals Ovarian Tumor Mitochondria Exhibit Abnormal Phenotypes and Blunted Associations with Biobehavioral Factors

2021 ◽  
Author(s):  
Snehal Bindra ◽  
Marlon McGill ◽  
Marina Triplett ◽  
Anisha Tyagi ◽  
Premal Thaker ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Respiratory Chain ◽  
Ovarian Tissue ◽  
Mitochondrial Respiratory Chain ◽  
Ovarian Tumors ◽  
Mitochondrial Content ◽  
Benign Tissue ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity ◽  
And Function

Abstract Tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and tumor mitochondria remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign and cancerous ovarian tissue in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n=1,435) showed that gene expression of specific mitochondrial proteins in ovarian tumors is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in 51 benign and 128 high-grade epithelial ovarian tumors revealed that compared to benign tissue, tumors exhibit 3.3-8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P<0.001) but similar mitochondrial DNA levels (-3.1%), documenting abnormal mitochondrial phenotypes in tumors. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r=-0.43 to 0.47). In contrast, serous tumors showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in ovarian tumors and warrant further research on the link between biobehavioral factors and mitochondria in cancer.

Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain

2011 ◽  
Vol 23 (3) ◽  
pp. 106-111 ◽  
Author(s):  
Tiago P. Freitas ◽  
Gislaine T. Rezin ◽  
Daiane B. Fraga ◽  
Morgana Moretti ◽  
Julia S. Vieira ◽  
...  
Keyword(s):  
Animal Model ◽  
Prefrontal Cortex ◽  
Respiratory Chain ◽  
Rebound Effect ◽  
Mitochondrial Respiratory Chain ◽  
Face Validity ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity ◽  
The Brain ◽  
Mitochondrial Respiratory

Objectives: Bipolar disorder (BD) is a mental illness associated with higher rates of suicide. The present study aims to investigate the brain mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Methods: Adult male Wistar rats received a single intracerebroventricular administration of ouabain (10−3 and 10−2 M) or vehicle. Locomotor activity was measured using the open field test. Mitochondrial respiratory chain activity was measured in the brain of rats 1 h and 7 days after ouabain administration.Results: Our results showed that spontaneous locomotion was increased 1 h and 7 days after ouabain administration. Complexes I, III and IV activities were increased in the prefrontal cortex, hippocampus and striatum immediately after the administration of ouabain, at the concentration of 10−3 and 10−2 M. Moreover, complex II activity was increased only in the prefrontal cortex at the concentration of 10−2 M. On the other hand, no significant alterations were observed in complex I activity 7 days after ouabain administration. However, an increase in complexes II, III and IV activities was observed only in the prefrontal cortex at the concentration of 10−2 M.Conclusion: Our findings suggest an increase in the activities of mitochondrial respiratory chain in this model of mania. A possible explanation is that these findings occur as a rebound effect trying to compensate for a decrease of ATP deprivation in BD. The present findings suggest that this model may present good face validity and a limitation in construct validity.

scholarly journals miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Feng Tian ◽  
Ping Tang ◽  
Zhilian Sun ◽  
Ruifen Zhang ◽  
Danhua Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
High Glucose ◽  
Mitochondrial Respiratory Chain ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
Complex Activity ◽  
Adipose Tissue Macrophages ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity

Objective. Type 2 diabetes mellitus (T2DM) is featured by insulin resistance and lipid metabolism dysregulation. A large number of miRNAs were identified in exosomes derived from adipose tissue macrophages associated with T2DM pathogenesis, but its pathogenic roles remain unknown. This study is aimed at investigating the function of miR-210 in diabetic obesity. Methods. Exosomes from mouse macrophage RAW264.7 cells were characterized by electron microscopy, combined with biomarker expression by western blot. Expression of miR-210 was determined by quantitative RT-PCR. Glucose uptake was measured by a fluorometric method, and the mitochondrial respiratory chain activity was evaluated by ELISA. The target gene of miR-210 was validated by dual-luciferase reporter and pull-down assays. A mouse obese diabetic model was established by a high-fat diet and streptozocin treatment. Results. miR-210 was highly expressed in exosomes derived from high glucose-induced macrophage RAW264.7 cells. Macrophage-derived exosomes impaired glucose uptake and mitochondrial CIV complex activity and suppressed NADH dehydrogenase ubiquinone 1 alpha subcomplex 4 (NDUFA4) expression in 3T3-L1 adipocytes. miR-210 directly bind with mRNA sequences of NDUFA4 gene. Inhibition of miR-210 mitigated the effects of macrophage-derived exosomes on the glucose uptake and complex IV (CIV) activity in 3T3-L1 adipocytes, and NDUFA4 overexpression offset the inhibition of glucose uptake and CIV activity by macrophage-derived exosomes. Furthermore, mice with miR-210 knockout showed greatly repressed diabetic obesity development. Conclusion. miR-210 derived from adipose tissue macrophages promotes mouse obese diabetes pathogenesis by regulating glucose uptake and mitochondrial CIV activity through targeting NDUFA4 gene expression.

scholarly journals Multi-Tissue DNA Methylation Remodeling at Mitochondrial Quality Control Genes According to Diet in Rat Aging Models

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 460 ◽  
Author(s):  
Patrizia D’Aquila ◽  
Francesco De Rango ◽  
Francesco Guarasci ◽  
Maurizio Mandalà ◽  
Andrea Corsonello ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Quality Control ◽  
Mitochondrial Dynamics ◽  
Epigenetic Modifications ◽  
Tissue Type ◽  
Mitochondrial Quality Control ◽  
Low Calorie ◽  
Low Calorie Diet ◽  
Calorie Diet ◽  
Methylation Patterns

An adequate mitochondrial quality control system ensures the maintenance of a healthy mitochondrial pool so as to slow down the progressive accumulation of damage affecting mitochondrial function during aging and diseases. The amount and quality of nutrients availability were demonstrated to induce a process of bioenergetics adaptation by influencing the above system via epigenetic modifications. Here, we analyzed DNA samples from differently-aged rats fed a standard or low-calorie diet to evaluate tissue-specific changes in DNA methylation of CpG sites falling within Polg, Polg2, Tfam, Fis1, and Opa1 genes. We found significant changes according to age and tissue type and the administration of the low-calorie diet is responsible for a prevalent increase in DNA methylation levels. Particularly, this increase was more appreciable when this diet was administered during adulthood and at old age. Regression analysis demonstrated that DNA methylation patterns of the analyzed genes were negatively correlated with their expression levels. Data we obtained provide the first evidence about changes in DNA methylation patterns of genes involved in the mitochondrial biogenesis in response to specific diets and demonstrated that epigenetic modifications are involved in the modulation of mitochondrial dynamics driven by age and nutrition.

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