mitochondria

摘要： Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope with this high energy demand.We previously showed that in adult zebrafish,subjected to an optic nerve crush,an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal repair.We postulate a‘dendrites for regeneration’paradigm that might be linked to intraneuronal mitochondrial reshuffling,as ganglion cells likely have insufficient resources to maintain dendrites and restore axons simultaneously.Here,we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments(dendrites,somas,and axons)during the regenerative process.Optic nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction,whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal regrowth.Upon dendritic regrowth in the retina,mitochondrial density inside the retinal dendrites returned to baseline levels.Moreover,a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve damage.Taken together,these findings suggest that during optic nerve injury-induced regeneration,mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.

摘要： Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.Dysregulation of Kinesin-family-member 5α(Kif5α),a neuron-specific isoform of heavy chain kinesin family,has been described in several neurological disorders,in humans and animal models,including ALS.In this study,we determined Kif5αexpression by gene sequencing,quantitative reverse transcription-polymerase chain reaction,and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn.Further,we observed the distribution of Kif5αand mitochondria along motor neuronal branches by confocal imaging.Our results showed that Kif5αexpression was greatly dysregulated in wobbler mice,which resulted in altered distribution of Kif5αalong motor neuronal branches with an abnormal mitochondrial distribution.Thus,our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level,like misallocation of cytoskeletal proteins or organelles like mitochondria.

摘要： By controlling the proper folding of proteins imported into mitochondria and ensuring crosstalk between the reticulum and mitochondria to modulate intra cellular calcium fluxes.Mortalin is a chaperone protein that plays crucial roles in neuronal homeostasis and activity.Howeve r,its expression and stability are strongly modified in response to cellular stresses,in particular upon alte red oxidative conditions during neurodegeneration.Here,we report and discuss the abundant literature that has highlighted its contribution to the pathophysiology of Parkinson's disease,as well as its therapeutic and prognostic potential in this still incurable pathology.

摘要： In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that have a variety of functions in ensuring cellular health and homeostasis. The plethora of mitochondrial functionalities confers them an intrinsic susceptibility to internal and external stressors(such as mutation accumulation or environmental toxins), particularly so in long-lived postmitotic cells such as neurons. Thus, it is reasonable to postulate an involvement of mitochondria in aging-associated neurological disorders, notably neurodegenerative pathologies including Alzheimer’s disease and Parkinson’s disease. On the other hand, biological effects resulting from neurodegeneration can in turn affect mitochondrial health and function, promoting a feedback loop further contributing to the progression of neuronal dysfunction and cellular death. This review examines state-of-the-art knowledge, focus on current research exploring mitochondrial health as a contributing factor to neuroregeneration, and the development of therapeutic approaches aimed at restoring mitochondrial homeostasis in a pathological setting.

摘要： Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.

摘要： Epilepsy is synonymous with individuals suffering repeated“fits”or seizures.The seizures are triggered by bursts of abnormal neuronal activity,across either the cerebral cortex and/or the hippocampus.In addition,the seizure sites are characterized by considerable neuronal death.Although the factors that generate this abnormal activity and death are not entirely clear,recent evidence indicates that mitochondrial dysfunction plays a central role.Current treatment options include drug therapy,which aims to suppress the abnormal neuronal activity,or surgical intervention,which involves the removal of the brain region generating the seizure activity.However,~30%of patients are unresponsive to the drugs,while the surgery option is invasive and has a morbidity risk.Hence,there is a need for the development of an effective non-pharmacological and non-invasive treatment for this disorder,one that has few side effects.In this review,we consider the effectiveness of a potential new treatment for epilepsy,known as photobiomodulation,the use of red to near-infrared light on body tissues.Recent studies in animal models have shown that photobiomodulation reduces seizure-like activity and improves neuronal survival.Further,it has an excellent safety record,with little or no evidence of side effects,and it is non-invasive.Taken all together,this treatment appears to be an ideal treatment option for patients suffering from epilepsy,which is certainly worthy of further consideration.

摘要： BACKGROUND:Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury.Mesenchymal stem cell(MSC)transplantation is used to reduce tissue damage,but exosomes are more stable and highly conserved than MSCs.This study was conducted to investigate the therapeutic effects of MSC-derived exosomes(MSC-Exo)on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R),and to explore the underlying mechanisms.METHODS:Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment,with or without MSC-Exo treatment.Exosomal integration,cell viability,mitochondrial membrane potential,and generation of reactive oxygen species(ROS)were examined.Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nickend labeling(TUNEL)staining was performed to detect neuronal apoptosis.Moreover,mitochondrial function-associated gene expression,Nrf2 translocation,and expression of downstream antioxidant proteins were determined.RESULTS:MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation(P<0.05).The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus(2.14±0.65 vs.5.48±1.09,P<0.01)and increased the intracellular expression of antioxidative proteins,including superoxide dismutase and glutathione peroxidase(17.18±0.97 vs.14.40±0.62,and 20.65±2.23 vs.16.44±2.05,respectively;P<0.05 for both).OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial functionassociated genes,such as PINK,DJ1,LRRK2,Mfn-1,Mfn-2,and OPA1.The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons.CONCLUSIONS:MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons.Therefore,MSCExo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.

摘要： Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica were used as explants. Mitochondrial structure and function, caspase-3-like protease activity, hydrogen peroxide metabolism, and nitric oxide accumulation induced by high concentrations of sucrose and plant growth regulators were studied. The results show that plant growth regulators induced somatic embryogenesis and also promoted explant browning. High sucrose concentrations had similar effects. High concentrations of sucrose and plant growth regulators led to the accumulation of hydrogen peroxide and nitric oxide which induced changes in mitochondrial structure and function such as modifications in mitochondrial morphology, increased membrane permeability, decreased membrane potential, and the release of cytochrome c into the cytoplasm. An increase in caspase-3-like protease activity triggered programmed cell death in some browning explant cells. During somatic embryogenesis there were increased activities of superoxide dismutase, peroxidase, and catalase, which are associated with hydrogen peroxide metabolism and jointly maintain reactive oxygen species levels. Intracellular nitric oxide synthase and nitrate reductase activities were not significantly correlated with nitric oxide content. Instead, intracellular nitric oxide may be derived from non-enzymatic reactions. Our results indicate that hydrogen peroxide and nitric oxide may function as signals, playing key roles in somatic embryogenesis and programmed cell death of explant cells of F. mandshurica. The interaction between nitric oxide and reactive oxygen species determines the occurrence of programmed cell death in explant cells;somatic embryogenesis and programmed cell death are positively regulated by hydrogen peroxide. However, the regulation of nitric oxide is complex.

摘要： Nicotinamide adenine dinucleotide (NAD) oscillation was observed when the isolated mitochondria were immersed in a pyruvate solution. In addition, when an adenosine diphosphate (ADP) was added to the mitochondrial suspension containing pyruvate, adenosine triphosphate (ATP) oscillation was observed as well as NADH oscillation. At this time, the pH within mitochondria also oscillated. It was found that the oscillatory reaction of NADH caused by the membrane permeation of pyruvate continues, causing the oscillation of NADH and H+ in the subsequent reactions. The pH oscillation led to the ATP oscillation. It is considered that the oscillatory reaction caused by the gradual entry of pyruvate into mitochondria was thought to be carried over to both the citric acid cycle and the respiratory chain, ultimately leading to the ATP oscillation in oxidative phosphorylation. Similarly, it was found that membrane permeation of malate causes the gradual occurrence of NADH, at which point NADH oscillates, followed by an oscillatory reaction of the respiratory chain, and finally ATP oscillation. It was found that the oscillations of NADH and ATP occur without going through the citric acid cycle. Oscillations of NADH and other intermediates in both the citric acid cycle and respiratory chain were also confirmed by experiments using semipermeable membranes. These results support our hypothesis that the gradual entry of the substrate by membrane permeation triggers an oscillatory reaction of the enzyme, which is also carried over to subsequent reactions.

摘要： Recent studies have demonstrated a new role for Klf10, a Krüppel-like transcription factor, in skeletal muscle, specifically relating to mitochondrial function. Thus, it was of interest to analyze additional tissues that are highly reliant on optimal mitochondrial function such as the cerebellum and to decipher the role of Klf10 in the functional and structural properties of this brain region. In vivo (magnetic resonance imaging and localized spectroscopy, behavior analysis) and in vitro (histology, spectroscopy analysis, enzymatic activity) techniques were applied to comprehensively assess the cerebellum of wild type (WT) and Klf10 knockout (KO) mice. Histology analysis and assessment of locomotion revealed no significant difference in Klf10 KO mice. Diffusion and texture results obtained using MRI revealed structural changes in KO mice characterized as defects in the organization of axons. These modifications may be explained by differences in the levels of specific metabolites (myo-inositol, lactate) within the KO cerebellum. Loss of Klf10 expression also led to changes in mitochondrial activity as reflected by a significant increase in the activity of citrate synthase, complexes I and IV. In summary, this study has provided evidence that Klf10 plays an important role in energy production and mitochondrial function in the cerebellum.

摘要： Millimeter wave (MW) is an electromagnetic wave with a wavelength between 1 and 10 mm and a frequency of 30～300 GHz that can evoke multiple biological effects, both locally and globally. MW has been broadly used in clinical medicine. Although our previous work demonstrated that MW can inhibit sodium nitroprussiate (SNP)-induced apoptosis in chondrocytes, the precise mechanism of the anti-apoptotic activity remains to be elucidated.In this report, we investigated the cellular effects of MW in 5NP-induced apoptotic chondrocytes. We found that MW treatment could inhibit an SNP-induced mitochondrion-dependent pathway of apoptosis. MW treatment inhibited the loss of plasma membrane asymmetry(externalization of phosphatidylserine)，collapse of mitochondria) membrane potential，and activation of caspase-9 and caspase-3.Taken together, these results suggest that MW inhibits the mitochondrion-dependent pathway of apoptosis in chondrocytes and this may, in part，explain its clinical effect in the treatment of osteoarthritis.

摘要： To explore the role of NO and sulfhydryl on pathogenesis of endotoxemia in goats,48 goats were divided randomly into 4 groups of A,B,C and D with 12 goats in each group.Group A was normal control ;Group B was LPS group; Group C was LPS+AG group; Group Dwas AG group, each of groups is divided into 3h Slaughter group after the injection of LPS and6h group After injection of LPS. the changes of the content of MDA,total sulfhydryl (T-SH),protein SH (PB-SH) and non-protein SH (NP-SH) and the activity of nitric oxide synthase(TNOS),inducible nitric oxide synthase (iNOS)and nitric oxide(NO)level in myocardialmitochondria were Detected. The results showed that when the goat endotoxemia the content oftotal sulfhydryl,protein SH,non-protein SH in myocardial mitochondrial decreased,the content ofMDA and the activity of nitric oxide synthase,inducible Nitric oxide synthase and nitric oxidelevel in myocardial mitochondrial significantly increased. Compared with the Lps group thesituation of aminoguanidine treatment group was significantly improved. The results indicatedthat,lipid peroxidation damage in the goat caused by the over-produced NO played an importantrole in the pathogenesis of endotoxemia. Aminoguanidine can effectivly antagonism lipidperoxidation damage.

摘要： Copper,an essential trace element for animals,is also essential for mitochondrialfunction,it is a prosthetic cofaetor for Cu/Zn-SOD,COX and monoamine oxidase (MAO),whichare common exist in mitochondria. In this study,experiment was performed to examine the effectof dietary copper supplementation on mitoehondrial function of liver in broiler chicken. Onehundred and sixty 1-day-old Cobb 500 broilers (Gallus domesticus,BW =43±0.32 g) werestratified by weight and randomly assigned to four dietary treatments of 40 broilers each,whichcontained 11 (control),110,220 and 330 mg of supplemental Cu/kg DM as CuSO4. All of theexperimental broilers were fed with corn-soybean meal containing supplemental copper for 60days; Liver mitoehondrial function of broiler chicken was recorded on days old of 12,24,36,48and 60. Copper supplementation had no significant influence on mitochondrial function (RCR andP/O) and mitoehondrial complex (Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅴ) in the treatment group supplemented with 11 mgCu/kg DM (P > 0.05). The supplement providing 110 mg Cu/kg DM increased mitochondrialfunction and the activities of complex Ⅰ-Ⅴ and had significant difference after 36 day-oldcompared with other groups (P0.05). Cu accumulation in liver and mitochondrial H2O2 production were increased (P < 0.05) byall Cu supplemented treatments during the feeding trail with the increase of dietary level of Cu inthe diet of birds,especially in the treatment group supplemented with 220 mg Cu/kg DM and 330mg Cu/kg DM. In conclusion,supplementation of the basal diet with 110 mg Cu/kg DM enhancedmitochondrial function and the activities of mitochondrial complex,but high dietary copper (with220 mg Cu/kg DM and 330 mg Cu/kg DM) appears to undermine the liver mitochondrial functionand complex activities except for complex Ⅳ which had more resistant to high liver copperaccumulation. There were increases in liver copper accumulation and mitochondrial H2O2production with the increase of dietary level of Cu in the diet of birds,the results of these studiesprovide insight into understanding subcellular mechanisms associated with the dietary copperoxicity in birds.

摘要： The endotoxemia,which is one of the fatal syndromes in clinical medicine science,causes human or animals multiple organ dysfunction syndromes due to a large number of freeradicals and cellular lipid peroxidation when the inherent antioxygen capability is depressed. It isknown that melatonin (MT) is the most effective antioxidant. The purpose of this experiment wasstudying the free radical metabolism in liver mitochondria of goats induced by lipoplysaccaride(LPS),evaluating the effect of MT treatment,and finally,obtaining some certain relationshipbetween LPS and free radical in hepatic mitochondria. 48 healthy goats (10±1.2 kg) wererandomly divided into four groups: saline/control group,LPS group,MT+ LPS group and MTgroup. Different treatments should be applied before the goats were killed in each group,and thencut the liver out of goats and isolated for mitochondria. Later,the respiration control rate (RCR),the ADP:O ratio,the oxidative phosphorylation ratio (OPR) and the concentration of H2O2 weredetermined. The result showed that: during endotoxemia,the electron leakage of livermitochondria increased in complex Ⅰ,Ⅲ and Ⅴ followed by decreasing of RCR,O/P and OPR.Melatonin attenuated the injury described previously. Conclusion: melatonin prevent mitochondriafrom oxidation attacks through decreasing the electron leakage of complex Ⅰ,Ⅲ and Ⅴ andincreasing the RCR,O/P and OPR.