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1.
Acta Physiologica Sinica ; (6): 1025-1034, 2021.
Article in Chinese | WPRIM | ID: wpr-921307

ABSTRACT

Cells selectively scavenge redundant or damaged mitochondria by mitophagy, which is an important mechanism of mitochondrial quality control. Recent studies have shown that mitophagy is mainly regulated by autophagy-related genes (Atgs) in yeast cells, while mitochondrial membrane associated proteins such as PTEN-induced putative kinase 1 (PINK1), NIX/BNIP3L, BNIP3, FUN14 domain containing 1 (FUNDC1), FKBP8/FKBP38, Bcl-2-like protein 13 (Bcl2L13), nucleotide binding domain and leucine-rich-repeat-containing proteins X1 (NLRX1), prohibitin 2 (PHB2) and lipids such as cardiolipin (CL) are the key mitophagic receptors in mammalian cells, which can selectively recognize damaged mitochondria, recruit them into isolation membranes by binding to microtubule-associated protein 1 light chain 3 (LC3) or γ-aminobutyric acid receptor-associated protein (GABARAP), and then fuse with lysosomes to eliminate the trapped mitochondria. This article reviews recent research progress of mitophagy-related receptor proteins.


Subject(s)
Animals , Apoptosis Regulatory Proteins , Autophagy , Microtubule-Associated Proteins , Mitochondria , Mitochondrial Proteins/genetics , Mitophagy
2.
Journal of Integrative Medicine ; (12): 537-544, 2021.
Article in English | WPRIM | ID: wpr-922525

ABSTRACT

OBJECTIVE@#Mitophagy is known to contribute towards progression of Parkinson's disease. Korean red ginseng (KRG) is a widely used medicinal herb in East Asia, and recent studies have reported that KRG prevents 1-methyl-4-phenylpyridinium ion (MPP@*METHODS@#SH-SY5Y cells were incubated with KRG for 24 h, and subsequently exposed to MPP@*RESULTS@#MPP@*CONCLUSION@#KRG effectively prevents MPP


Subject(s)
1-Methyl-4-phenylpyridinium/toxicity , Apoptosis , Cell Line, Tumor , Mitochondria , Mitophagy , Panax , Reactive Oxygen Species
3.
Chinese Medical Journal ; (24): 2599-2609, 2020.
Article in English | WPRIM | ID: wpr-877854

ABSTRACT

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.


Subject(s)
Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Stress , Humans , Mitochondria , Mitochondrial Membranes/metabolism , Mitophagy , Reperfusion Injury/metabolism
4.
Article in Chinese | WPRIM | ID: wpr-880798

ABSTRACT

OBJECTIVE@#To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG).@*METHODS@#Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 μmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and @*RESULTS@#RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I (@*CONCLUSIONS@#RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.


Subject(s)
Animals , Cinnamates , Depsides , Glucose , Hypertrophy , Mitophagy , Myocytes, Cardiac , Protein Kinases , Rats , Reactive Oxygen Species , Ubiquitin-Protein Ligases/genetics
5.
Acta Physiologica Sinica ; (6): 475-487, 2020.
Article in Chinese | WPRIM | ID: wpr-827039

ABSTRACT

The abnormality of mitochondrial morphology and function is closely related to the pathogenesis of many diseases. Mitochondrial fusion-fission dynamics are critical to maintain normal morphology, distribution and quantity of mitochondria, and ensure the normal activity of cells. In addition, mitochondrial autophagy (mitophagy) plays an important role in maintaining mitochondrial quality by degrading aging or damaged mitochondria. Many previous studies showed that mitochondrial dynamics and mitophagy can regulate each other to sustain mitochondrial network homeostasis. Clarifying regulatory mechanisms of mitochondrial dynamics and mitophagy is of great significance for revealing the molecular mechanism of various diseases and for the development of new drugs targeting mitochondrial dynamics proteins or mitophagy regulatory proteins. This review focuses on the role of mitochondrial dynamics and mitophagy in mitochondrial quality control, regulatory mechanism, the interplay between those two processes, and their roles in human-related diseases.


Subject(s)
Autophagy , Humans , Mitochondria , Mitochondrial Dynamics , Mitochondrial Proteins , Mitophagy
6.
Korean Circulation Journal ; : 395-405, 2020.
Article in English | WPRIM | ID: wpr-816678

ABSTRACT

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.


Subject(s)
Adenosine Triphosphate , Cardiovascular Diseases , Cause of Death , Heart Failure , Heart , Homeostasis , Mitochondria , Mitophagy , Organelles , Quality Control , Spermidine , Unfolded Protein Response
7.
Article in English | WPRIM | ID: wpr-763048

ABSTRACT

Brain aging is an inevitable process characterized by structural and functional changes and is a major risk factor for neurodegenerative diseases. Most brain aging studies are focused on neurons and less on astrocytes which are the most abundant cells in the brain known to be in charge of various functions including the maintenance of brain physical formation, ion homeostasis, and secretion of various extracellular matrix proteins. Altered mitochondrial dynamics, defective mitophagy or mitochondrial damages are causative factors of mitochondrial dysfunction, which is linked to age-related disorders. Etoposide is an anti-cancer reagent which can induce DNA stress and cellular senescence of cancer cell lines. In this study, we investigated whether etoposide induces senescence and functional alterations in cultured rat astrocytes. Senescence-associated β-galactosidase (SA-β-gal) activity was used as a cellular senescence marker. The results indicated that etoposide-treated astrocytes showed cellular senescence phenotypes including increased SA-β-gal-positive cells number, increased nuclear size and increased senescence-associated secretory phenotypes (SASP) such as IL-6. We also observed a decreased expression of cell cycle markers, including Phospho-Histone H3/Histone H3 and CDK2, and dysregulation of cellular functions based on wound-healing, neuronal protection, and phagocytosis assays. Finally, mitochondrial dysfunction was noted through the determination of mitochondrial membrane potential using tetramethylrhodamine methyl ester (TMRM) and the measurement of mitochondrial oxygen consumption rate (OCR). These data suggest that etoposide can induce cellular senescence and mitochondrial dysfunction in astrocytes which may have implications in brain aging and neurodegenerative conditions.


Subject(s)
Aging , Animals , Astrocytes , Brain , Cellular Senescence , Cell Cycle , Cell Line , DNA , Etoposide , Extracellular Matrix Proteins , Homeostasis , Interleukin-6 , Membrane Potential, Mitochondrial , Mitochondria , Mitophagy , Mitochondrial Dynamics , Neurodegenerative Diseases , Neurons , Neuroprotection , Oxygen Consumption , Phagocytosis , Phenotype , Rats , Risk Factors , Wound Healing
8.
Article in English | WPRIM | ID: wpr-713768

ABSTRACT

BACKGROUND: Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. METHODS: In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. RESULTS: Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. CONCLUSION: These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.


Subject(s)
Cell Death , Cell Survival , Cyclic Nucleotide Phosphodiesterases, Type 4 , Emphysema , Epithelial Cells , L-Lactate Dehydrogenase , Lung , Mitochondria , Mitophagy , Mitochondrial Dynamics , Pulmonary Disease, Chronic Obstructive , Smoke , Tobacco Products , Tobacco Use
9.
Article in Chinese | WPRIM | ID: wpr-300818

ABSTRACT

Autophagy is fundamental to maintain cellular homeostasis. As one kind of the most well-studied selective autophagy, autophagy of mitochondria (mitophagy)is crucial for the clearance of damaged mitochondria. Mitophagy dysfunction has been proved to be closely associated with many human diseases. Nix is a key protein for mitophagy during the maturation of reticulocytes. However, the detailed molecular mechanisms underlying Nix-mediated mitophagy are not fully understood. This article summarizes three possible working models of Nix in mitophagy induction. Firstly, Nix can interplay with Parkin, another important protein for mitophagy, to initiate mitophagy. Secondly, Nix can serve as a receptor for autophagy machinery by interacting with Atg8 family through its LIR motif. Finally, as a BH3-only protein, Nix can compete with Beclin-1 to bind other members of Bcl-2 family resulting in increased free Beclin-1 in cytosol, which further promotes autophagy flux.


Subject(s)
Autophagy , Genetics , Physiology , Autophagy-Related Protein 8 Family , Physiology , Beclin-1 , Physiology , Membrane Proteins , Physiology , Mitochondria , Genetics , Physiology , Mitophagy , Genetics , Physiology , Protein Interaction Domains and Motifs , Proto-Oncogene Proteins , Physiology , Proto-Oncogene Proteins c-bcl-2 , Tumor Suppressor Proteins , Physiology , Ubiquitin-Protein Ligases , Physiology
10.
Article in Chinese | WPRIM | ID: wpr-297219

ABSTRACT

Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system. Neural cells rely on autophagy to control protein quality and eliminate the damaged mitochondria, and under normal circumstances, mitophagy can protect the neural cells. Mutations in genes related to mitophagy may cause the development and progression of neurodegenerative diseases. An understanding of the role of mitophagy in nervous system diseases may provide new theoretical bases for clinical treatment. This article reviews the research advances in the relationship between mitophagy and different types of nervous system diseases.


Subject(s)
Apoptosis , Autophagy , Physiology , Humans , Mitophagy , Nervous System Diseases , Neurodegenerative Diseases
11.
Article in English | WPRIM | ID: wpr-728755

ABSTRACT

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in O₂ respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle.


Subject(s)
Adenosine Triphosphate , Apoptosis , Energy Metabolism , Glucose , Homeostasis , Lipid Metabolism , Metabolism , Mitochondria , Mitophagy , Mitochondrial Dynamics , Muscle, Skeletal , Obesity , Organelle Biogenesis , Organelles , Oxidative Phosphorylation , Oxidative Stress , Respiration
12.
Article in Chinese | WPRIM | ID: wpr-351368

ABSTRACT

<p><b>OBJECTIVE</b>To investigate mitophagy in an animal model of hypoxic-ischemic brain damage (HIBD) and its role in HIBD.</p><p><b>METHODS</b>A total of 120 neonatal Sprague-Dawley rats aged 7 days were divided into three groups: sham-operation, HIBD, and autophagy inhibitor intervention (3MA group). The rats in the HIBD group were treated with right common carotid artery ligation and then put in a hypoxic chamber (8% oxygen and 92% nitrogen) for 2.5 hours. Those in the 3MA group were given ligation and hypoxic treatment at 30 minutes after intraperitoneal injection of 2 μL 3MA. Those in the sham-operation group were not given ligation or hypoxic treatment. Single cell suspension was obtained from all groups after model establishment. Immunofluorescence localization was performed for mitochondria labeled with MitoTracker, autophagosomes labeled with LysoTracker, and autophagy labeled with LC3 to observe mitophagy. After staining with the fluorescent probe JC-1, flow cytometry was used to measure mitochondrial membrane potential. TTC staining was used to measure infarct volume. Cytoplasmic proteins in cortical neurons were extracted, and Western blot was used to measure the expression of mitophagy-related proteins.</p><p><b>RESULTS</b>Compared with the sham-operation group, the HIBD group had a significant reduction in mitochondrial membrane potential (P<0.05), a significant increase in mitophagy (P<0.05), a significant increase in the expression of the proteins associated with the division of the mitochondrial Drp1 and Fis1 (P<0.05), and a significant reduction in the expression of the mitochondrial outer membrane protein Tom20 and the mitochondrial inner membrane protein Tim23 (P<0.05). Compared with the HIBD group, the 3MA group had a significantly greater reduction in mitochondrial membrane potential (P<0.05), but showed significantly reduced mitophagy (P<0.05). In addition, the 3MA group had a significantly increased degree of cerebral infarction compared with the HIBD group (P<0.05).</p><p><b>CONCLUSIONS</b>HIBD can increase the degree of mitophagy, and the inhibition of mitophagy can aggravate HIBD in neonatal rats.</p>


Subject(s)
Animals , Animals, Newborn , Female , Hypoxia-Ischemia, Brain , Male , Mitophagy , Physiology , Rats , Rats, Sprague-Dawley
13.
Article in Korean | WPRIM | ID: wpr-205041

ABSTRACT

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide (NAD+) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.


Subject(s)
Adenosine Triphosphate , Calcium , Cardiolipins , DNA, Mitochondrial , Homeostasis , Immunity, Innate , Inflammasomes , Inflammation , Metabolic Networks and Pathways , Mitochondria , Mitophagy , NAD , Reactive Oxygen Species
14.
Protein & Cell ; (12): 25-38, 2017.
Article in English | WPRIM | ID: wpr-757373

ABSTRACT

Mitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification of FUNDC1 affects its binding affinity for LC3B and regulates selective mitophagy. However, the structural basis of this regulation mechanism remains unclear. Here, we present the crystal structure of LC3B in complex with a FUNDC1 LIR peptide phosphorylated at Ser17 (pS), demonstrating the key residues of LC3B for the specific recognition of the phosphorylated or dephosphorylated FUNDC1. Intriguingly, the side chain of LC3B Lys49 shifts remarkably and forms a hydrogen bond and electrostatic interaction with the phosphate group of FUNDC1 pS. Alternatively, phosphorylated Tyr18 (pY) and Ser13 (pS) in FUNDC1 significantly obstruct their interaction with the hydrophobic pocket and Arg10 of LC3B, respectively. Structural observations are further validated by mutation and isothermal titration calorimetry (ITC) assays. Therefore, our structural and biochemical results reveal a working model for the specific recognition of FUNDC1 by LC3B and imply that the reversible phosphorylation modification of mitophagy receptors may be a switch for selective mitophagy.


Subject(s)
Crystallography, X-Ray , Membrane Proteins , Chemistry , Metabolism , Microtubule-Associated Proteins , Chemistry , Metabolism , Mitophagy , Mitochondrial Proteins , Chemistry , Metabolism , Peptides , Chemistry , Metabolism , Phosphorylation , Protein Structure, Quaternary
15.
Acta Pharmaceutica Sinica ; (12): 33-38, 2016.
Article in Chinese | WPRIM | ID: wpr-320020

ABSTRACT

Autophagy is a physiological process which delivers the mutant cytoplasmic proteins and dysfunctional subcellular organs into lysosomes for degradation to generate fuel in the deficiency conditions. It is mainly classified into macroautophagy, microautophagy and chaperon-mediated autophagy (CMA), as well as the selective autophagy such as mitophagy and aggrephagy. This review mainly introduces the key molecular markers of macroautophagy, CMA and mitophagy.


Subject(s)
Autophagy , Humans , Lysosomes , Mitophagy , Molecular Chaperones
16.
Acta Pharmaceutica Sinica ; (12): 59-67, 2016.
Article in Chinese | WPRIM | ID: wpr-320016

ABSTRACT

Nitrites play multiple characteristic functions in invasion and metastasis of hepatic cancer cells, but the exact mechanism is not yet known. Cancer cells can maintain the malignant characteristics via clearance of excess mitochondria by mitophagy. The purpose of this article was to determine the roles of nitrite, reactive oxygen species (ROS) and hypoxia inducing factor 1 alpha (HIF-1 α) in mitophagy of hepatic cancer cells. After exposure of human hepatocellular carcinoma SMMC-7721 cells to a serial concentrations of sodium nitrite for 24 h under normal oxygen, the maximal cell vitality was increased by 16 mg x (-1) sodium nitrite. In addition, the potentials of migration and invasion for SMMC-7721 cells were increased significantly at the same time. Furthermore, sodium nitrite exposure displayed an increase of stress fibers, lamellipodum and perinuclear mitochondrial distribution by cell staining with Actin-Tracker Green and Mito-Tracker Red, which was reversed by N-acetylcysteine (NAC, a reactive oxygen scavenger). DCFH-DA staining with fluorescent microscopy showed that the intracellular level of ROS concentration was increased by the sodium nitrite treatment. LC3 immunostaining and Western blot results showed that sodium nitrite enhanced cell autophagy flux. Under the transmission electron microscopy (TEM), more autolysosomes formed after sodium nitrite treatment and NAC could prevent autophagosome degradation. RT-PCR results indicated that the expression levels of COX I and COXIV mRNA were decreased significantly after sodium nitrite treatment. Meanwhile, laser scanning confocal microscopy showed that sodium nitrite significantly reduced mitochondrial mass detected by Mito-Tracker Green staining. The expression levels of HIF-1α, Beclin-1 and Bnip3 (mitophagy marker molecular) increased remarkably after sodium nitrite treatment, which were reversed by NAC. Our results demonstrated that sodium nitrite (16 mg x L(-1)) increased the potentials of invasion and migration of hepatic cancer SMMC-7721 cells through induction of ROS and HIF-1α mediated mitophagy.


Subject(s)
Acetylcysteine , Pharmacology , Autophagy , Carcinoma, Hepatocellular , Pathology , Cell Line, Tumor , Cell Movement , Humans , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Liver Neoplasms , Pathology , Mitophagy , Neoplasm Invasiveness , Nitrites , Metabolism , Reactive Oxygen Species , Metabolism , Sodium Nitrite , Pharmacology
17.
Protein & Cell ; (12): 699-713, 2016.
Article in English | WPRIM | ID: wpr-757387

ABSTRACT

Mitochondria play a key role in various cell processes including ATP production, Ca homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insufficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.


Subject(s)
Animals , Brain Ischemia , Metabolism , Pathology , Humans , Mitophagy , Reactive Oxygen Species , Metabolism , Stroke , Metabolism , Pathology
18.
Article in English | WPRIM | ID: wpr-728512

ABSTRACT

This study surveys the improvement characteristics in old-aged muscular mitochondria by bio-active materials coated fabric (BMCF). To observe the effects, the fabric (10 and 30%) was worn to old-aged rat then the oxygen consumption efficiency and copy numbers of mitochondria, and mRNA expression of apoptosis- and mitophagy-related genes were verified. By wearing the BMCF, the oxidative respiration significantly increased when using the 30% materials coated fabric. The mitochondrial DNA copy number significantly decreased and subsequently recovered in a dose-dependent manner. The respiratory control ratio to mitochondrial DNA copy number showed a dose-dependent increment. As times passed, Bax, caspase 9, PGC-1alpha and beta-actin increased, and Bcl-2 decreased in a dose-dependent manner. However, the BMCF can be seen to have had no effect on Fas receptor. PINK1 expression did not change considerably and was inclined to decrease in control group, but the expression was down-regulated then subsequently increased with the use of the BMCF in a dose-dependent manner. Caspase 3 increased and subsequently decreased in a dose-dependent manner. These results suggest that the BMCF invigorates mitophagy and improves mitochondrial oxidative respiration in skeletal muscle, and in early stage of apoptosis induced by the BMCF is not related to extrinsic death-receptor mediated but mitochondria-mediated signaling pathway.


Subject(s)
Actins , Animals , fas Receptor , Apoptosis , Caspase 3 , Caspase 9 , DNA, Mitochondrial , Mitochondria , Mitophagy , Muscle, Skeletal , Oxygen Consumption , Rats , Respiration , RNA, Messenger
19.
São Paulo; s.n; s.n; 2014. 145 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-847279

ABSTRACT

Bicarbonato é uma importante espécie química para os seres vivos, sendo o principal tampão celular, alem de apresentar uma negligenciada atividade redox. Isquemia é um evento no qual existe inibição do aporte de nutrientes e oxigênio, sendo a reperfusão o retorno do fluxo de nutrientes e oxigênio, que é acompanhada por alta produção de radicais livres e morte celular. Nessa tese estudamos o efeito da presença de bicarbonato durante a isquemia-reperfusão. Em nosso modelo nós mantivemos o pH constante e modulamos a quantidade de bicarbonato enquanto células, órgãos e animais foram submetidos a isquemia-reperfusão. Utilizamos condições sem a presença de bicarbonato, a concentração basal sanguínea e uma concentração mais alta simulando o acúmulo de bicarbonato em condições isquêmicas. Nesses diversos modelos mostramos que a presença de bicarbonato aumenta o dano provocado por isquemia-reperfusão e provoca um aumento do acúmulo de proteínas oxidadas. A presença do bicarbonato não modifica a respiração, produção de espécies reativas de oxigênio, ou a morfologia mitocondrial, também não detectamos mudança na atividade do proteassoma e nos indicadores de autofagia geral. Entretanto detectamos um acúmulo de marcadores autofágicos na fração mitocondrial indicando inibição da mitofagia. Essa inibição foi confirmada ao detectarmos o acúmulo de uma proteína degradada especificamente por mitofagia enquanto não houve mudança em outra degradada pelo proteassoma. Além disso, ao inibirmos farmacologicamente a autofagia, reproduzimos o fenótipo causado pelo bicarbonato mesmo na sua ausência. Em conclusão, a presença de bicarbonato é deletéria em condições de isquemia/reperfusão devido a inibição da mitofagia


Bicarbonate is an important molecule in all living being, acting as the main cellular buffer. However, its biological and redox activity has been mostly neglected to date. Ischemia is an event in which an inhibition of nutrient availablity and oxygen flow occurs, while reperfusion is the return of nutrients and oxygen, accompanied of a burst of reactive oxygen species production and cell death. Here, we studied the effects of bicarbonate during cardiac ischemia-reperfusion. In our model, we kept the pH stable and changed the concentration of the bicarbonate. We then subjected cells, organs and animals to ischemia-reperfusion under conditions where there was no presence, basal blood concentration or a higher concentration of bicarbonate. In these diverse models, we found that the presence of bicarbonate increased damage after a ischemia-reperfusion, and promoted the accumulation of oxidized proteins. Bicarbonate did not change respiration, production of reactive oxygen species or the morphology of the mitochondria. There were also no changes in proteasome activity and in global autophagy markers, although there was an accumulation of mitophagy markers. We also found that mitophagy was responsible for the increased damage observed, since pharmacological inhibiting of autophagy abolished the increased damage caused by the presence of bicarbonate. In conclusion the presence of bicarbonate is deleterious in ischemia-reperfusion due mitophagy inhibition


Subject(s)
Animals , Male , Female , Rats , Bicarbonates/analysis , Carbon Dioxide/analysis , Ischemia/physiopathology , Mitochondria , Mitophagy , Reperfusion
20.
Article in Korean | WPRIM | ID: wpr-27590

ABSTRACT

Parkinson's disease (PD) is the second most common neurodegenerative motor disorder, affecting approximately 1% of the population aged > or =60 years. Recent investigations have shown that in addition to motor symptoms such as bradykinesia, resting tremor, and gait instability, PD also causes non-motor symptoms such as insomnia, constipation, depression, and dementia. Most PD cases occurred sporadically, but 5-10% is inherited as familial PD, and several PD-causative genes have been identified and intensively studied. Autophagy is a self-degrading mechanism of balancing the energy source in response to nutrient shortage and various stresses, and is a tightly regulated and complicated process that generates double-membrane organelles. Autophagy failure has recently been observed in both animal PD models and human PD patients. The intention of this review is to introduce recent findings regarding the relationship between causative genetic mutations in PD and autophagy, from a clinical perspective.


Subject(s)
Animals , Autophagy , Constipation , Dementia , Depression , Gait , Humans , Hypokinesia , Intention , Mitophagy , Organelles , Parkinson Disease , Sleep Initiation and Maintenance Disorders , Tremor
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