DigitalUM :: Browsing by Subject "Mitochondria"

Browsing by Subject "Mitochondria"

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Open Access
8-weeks training program attenuates mitochondrial oxidative stress in the liver of emotionally stressed rats
(Murcia : F. Hernández, 2006) Rosety-Rodriguez, M.; Ordóñez Muñoz, F.J.; Rosety, I.; Frias, L.; Rosety, M.A.; Rosety, J.M.; Rosety, M.A.
In recent years it has been shown that emotional stress induced by immobilization may change the balance between pro-oxidant and antioxidant factors inducing oxidative damage. On the other hand, contradictory views exist concerning the role of physical activity on redox metabolism. Consequently, the present work was designed to assess the influence of an 8-week moderate swimming training program in emotionally stressed rats. Sixty 1-month-old male albino Wistar rats weighing 125-135 g were used in this experimental study. They were divided into three groups, as Control (lot A; n=20), Stressed (lot B; n=20) and Stressed & Exercised (lot C; n=20). Rats were stressed by placing the animals in a 25 x 7 cm plastic bottle 1 h/day, 5 days a week for 8 weeks. Protein carbonyl content values in liver homogenates were significantly increased in stressed animals (0.58±0.02 vs 0.86±0.03; p=0.018) which clearly indicated that emotional stress was associated with oxidative stress. Ultrastructural alterations, predominantly mitochondrial swelling and the decrease of cristae number observed by electron microscopy represented direct evidence of membrane injury. The most striking feature of our study was that we also found differences between stressed rats and stressed rats that performed our 8 week training program. Consequently our results highlight the potential benefit of a moderate training program to reduce oxidative damage induced by emotional stress since it attenuated protein oxidation and mitochondrial alterations.
Open Access
Age-related changes in mitochondrial membrane composition of Nothobranchius furzeri. Comparison with a longer-living Nothobranchius species
(Springer Nature, 2019-02-15) Almaida Pagán, Pedro Francisco; Ortega-Sabater C.; Lucas-Sanchez A.; Gonzalez-Silvera D.; Martinez-Nicolas A.; Rol de Lama, María de los Ángeles; Mendiola P.; de Costa J.; Fisiología
Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging, especially during phases of high oxidative stress that result in molecular damage. Changes affecting lipid class or fatty acid (FA) compositions could affect phospholipid (PL) properties and alter mitochondrial function. In the present study, mitochondrial membrane PL compositions were analysed throughout the life-cycle of Nothobranchius furzeri, a species with explosive growth and one of the shortest-lived vertebrates. Mitochondrial PLs showed several changes with age. Proportions of total PLs and PC were reduced while an increase in PS, CL and PE was observed, mainly between the 2.5 and 5 months of fish age, the time during which animals doubled their weight. FA compositions of individual PLs in mitochondria were also significantly affected with age suggesting the existence of increasing damage to mitochondrial lipids during the life- cycle of N. furzeri that could be one of the main contributors to degraded mitochondrial function associated with aging. The peroxidation index values from N. furzeri mitochondrial PLs were significantly lower than those reported in N. rachovii, a species with a 2-fold longer life span than N. furzeri, which seems to contradict the membrane pacemaker theory of animal metabolism
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Age-related changes in mitochondrial membrane composition of Nothobranchius furzeri: comparison with a longer-living Nothobranchius species
(Springer, 2018-10-09) Almaida Pagán, Pedro Francisco; Ortega-Sabater, C; Lucas-Sanchez, A; Gonzalez Silvera, D; Martinez-Nicolas, A; Rol, M A; Mendiola, P; Costa, J. de; Chronobiology Lab, Department of Physiology, College of Biology, University of Murcia, Mare Nostrum Campus, IUIE, IMIB-Arrixaca, Murcia, Spain; Ciber Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain; Department of Cell Biology, College of Biology, University of Murcia, Murcia, Spain
Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging, especially during phases of high oxidative stress that result in molecular damage. Changes affecting lipid class or fatty acid (FA) compositions could affect phospholipid (PL) properties and alter mitochondrial function. In the present study, mitochondrial membrane PL compositions were analysed throughout the life-cycle of Nothobranchius furzeri, a species with explosive growth and one of the shortest-lived vertebrates. Mitochondrial PLs showed several changes with age. Proportions of total PLs and PC were reduced while an increase in PS, CL and PE was observed, mainly between the 2.5 and 5 months of fish age, the time during which animals doubled their weight. FA compositions of individual PLs in mitochondria were also significantly affected with age suggesting the existence of increasing damage to mitochondrial lipids during the life-cycle of N. furzeri that could be one of the main contributors to degraded mitochondrial function associated with aging. The peroxidation index values from N. furzeri mitochondrial PLs were significantly lower than those reported in N. rachovii, a species with a two-fold longer life span than N. furzeri, which seems to contradict the membrane pacemaker theory of animal metabolism.
Embargo
Age-related changes in mitochondrial membrane composition of nothobranchius rachovii
(Oxford University Press, 2013-05-17) Lucas-Sánchez, Alejandro; Almaida Pagán, Pedro Francisco; Tocher, Douglas R.; Mendiola, Pilar; Costa, Jorge de; Fisiología
Mitochondrial membrane composition may be a critical factor in the mechanisms of the aging process by influencing the propagation of reactions involved in mitochondrial function during periods of high stress. Changes affecting either lipid class or fatty acid compositions could affect phospholipid properties and alter mitochondrial function and cell viability In the present study, mitochondrial membrane phospholipid compositions were analyzed throughout the life cycle of Nothobranchius rachovii. Mitochondrial phospholipids showed several changes with age. Proportions of cardiolipin decreased and those of sphingomyelin increased between 11- and 14-month-old fish. Fatty acid compositions of individual phospholipids in mitochondria were also significantly affected with age. These data suggest increasing damage to mitochondrial lipids during the life cycle of N. rachovii that could be one of the main factors related with and contributing to degraded mitochondrial function associated with the aging process.
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Age-related changes in mitochondrial membrane composition of rainbow trout (Oncorhynchus mykiss) heart and brain
(Elsevier, 2012-05-22) Almaida Pagán, Pedro Francisco; Costa, J. de; Mendiola, P; Tocher, D R; Fisiología; Institute of Aquaculture, School of Natural Sciences, University of Stirling, Stirling FK9 4LA, Scotland, United Kingdom; Department of Physiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain
Membrane composition, particularly of mitochondria, could be a critical factor by determining the propaga-tion of reactions involved in mitochondrial function during periods of high oxidative stress such as rapid growth and aging. Considering that phospholipids not only contribute to the structural and physical properties of biological membranes, but also participate actively in cell signaling and apoptosis, changes affecting either class or fatty acid compositions could affect phospholipid properties and, thus, alter mitochondrial function and cell viability. In the present study, heart and brain mitochondrial membrane phospholipid compositions were analyzed in rainbow trout during the four first years of life, a period characterized by rapid growth and a sustained high metabolic rate. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and phospholipid class compositions of heart and brain mitochondria, and fatty acid compositions of individual phospholipid classes were determined. Rainbow trout heart and brain mitochon- dria showed different phospholipid compositions (class and fatty acid), likely related to tissue-specific functions. Furthermore, changes in phospholipid class and fatty acid compositions with age were also tissue-dependent. Heart mitochondria had lower proportions of cardiolipin (CL), phosphatidylserine (PS) and phosphatidylinositol, and higher levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) with age. Heart mitochondrial membranes became more unsaturated with age, with a significative increase of peroxidation index in CL, PS and sphingomyelin (SM). Therefore, heart mitochondria became more susceptible to oxidative damage with age. In contrast, brain mitochondrial PC and PS content decreased in 4-year-old animals while there was an increase in the proportion of SM. The three main phospholipid classes in brain (PC, PE and PS) showed decreased n−3 polyunsaturated fatty acids, docosahexaenoic acid and peroxidation index, which indicate a different response of brain mitochondrial lipids to rapid growth and maturation.
Open Access
Cellular and molecular mechanisms involved in the selective vulnerability of striatal projection neurons in Huntington`s disease
(Murcia : F. Hernández, 2006) Pérez-Navarro, E.; Canals, J.M.; Ginés, S.; Alberch, J.
Neurodegenerative disorders affecting the central nervous system, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s chorea (HD) and amyotrophic lateral sclerosis are characterized by the loss of selected neuronal populations. Another striking feature shared by these diseases is the deposition of proteinaceous inclusion bodies in the brain, which may be intracytoplasmatic or intranuclear, or even extracellular. However, the density and prevalence of aggregates are not always directly related to neurodegeneration. Although some of these diseases are the result of mutations in known proteins, with HD a clear example, the expression and location of the affected protein do not explain the selective neurodegeneration. Therefore, other intrinsic mechanisms, characteristic of each neuronal population, might be involved in the neurodegenerative process. In this review we focus on several proposed mechanisms such as excitotoxicity, mitochondrial dysfunction and altered expression of trophic factors, which could account for the pathogenesis of HD.
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Changes in tissue and mitochondrial membrane composition during rapid growth, maturation and aging in rainbow trout, Oncorhynchus mykiss
(Elsevier, 2012-01-16) Almaida Pagán, Pedro Francisco; Costa, J. de; Mendiola, P; Tocher, D R; Fisiología; Institute of Aquaculture, School of Natural Sciences, University of Stirling, Stirling FK9 4LA, Scotland, United Kingdom; Department of Physiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain
Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging processes, especially during phases of high oxidative stress that result in molecular damage. In the present study, liver and mitochondrial membrane phospholipid (PL) compositions were analyzed in rainbow trout during its four first years of life, a period characterized by rapid growth and high oxidative stress. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and PL compositions of whole liver and liver mitochondria, and fatty acid compositions of individual PL classes were determined. Liver mitochondrial membranes showed a PL composition different to that of the whole tissue suggesting adaptation of cell and subcellular membranes to specific functions. Individual PL had characteristic fatty acid compositions that were similar in whole liver and mitochondrial membranes. Whole liver and mitochondria showed increased lipid peroxidation with age along with changes in membrane PL fatty acid compositions. Most PL classes showed similar changes in fatty acid composition among the age groups, with reduced proportions of docosahexaenoic acid (DHA) and, generally, concomitantly increased levels of monounsaturated fatty acids, which together resulted in reduced peroxidation index (PIn). However, total polyunsaturated fatty acid (PUFA) content did not change significantly with age due to increased eicosapentaenoic acid, docosapentaenoic acid and, in most PL, increased n−6 PUFA. These results suggest there may be oxidation of PL DHA with compensatory mechanisms to maintain membrane fluidity and function. However, modification of fatty acid composition of specific PLs, such as cardiolipin, could affect the electron transport chain efficiency and propagate the oxidative reaction throughout the cell. In addition, both the content and fatty acid composition of sphingomyelin, which has been suggested as a possible mediator of cell dysfunction and apoptosis, changed with age differently to the other PL classes. Moreover, these changes showed different trends between mitochondria and whole liver. These data suggest there is marked oxidative stress associated with rapid growth and maturation in rainbow trout. Changes observed in membrane lipids point to their possible participation in the processes involved in this species response to oxidative stress and damage accumulation rate.
Open Access
Deactivation of the JNK Pathway by GSTP1 is essential to maintain sperm functionality
(Frontiers Media, 2021-02-25) Llavanera, Marc; Mateo-Otero, Yentel; Delgado-Bermúdez, Ariadna; Recuero, Sandra; Olives, Samuel; Barranco Cascales, Isabel; Yeste, Marc; Medicina y Cirugía Animal; Facultad de Veterinaria
Fifty percent of male subfertility diagnosis is idiopathic and is usually associated with genetic abnormalities or protein dysfunction, which are not detectable through the conventional spermiogram. Glutathione S-transferases (GSTs) are antioxidant enzymes essential for preserving sperm function and maintaining fertilizing ability. However, while the role of GSTP1 in cell signaling regulation via the inhibition of c-Jun N-terminal kinases (JNK) has been enlightened in somatic cells, it has never been investigated in mammalian spermatozoa. In this regard, a comprehensive approach through immunoblotting, immunofluorescence, computer-assisted sperm assessment (CASA), and flow cytometry analysis was used to characterize the molecular role of the GSTP1-JNK heterocomplex in sperm physiology, using the pig as a model. Immunological assessments confirmed the presence and localization of GSTP1 in sperm cells. The pharmacological dissociation of the GSTP1-JNK heterocomplex resulted in the activation of JNK, which led to a significant decrease in sperm viability, motility, mitochondrial activity, and plasma membrane stability, as well as to an increase of intracellular superoxides. No effects in intracellular calcium levels and acrosome membrane integrity were observed. In conclusion, the present work has demonstrated, for the first time, the essential role of GSTP1 in deactivating JNK, which is crucial to maintain sperm function and has also set the grounds to understand the relevance of the GSTP1-JNK heterocomplex for the regulation of mammalian sperm physiology.
Open Access
Dietary fatty acids affect mitochondrial phospholipid compositions and mitochondrial gene expression of rainbow trout liver at different ages
(Springer, 2014-11-15) Almaida Pagán, Pedro Francisco; De Santis, C; Rubio-Mejia, O L; Tocher, D R; Fisiología
Mitochondria are among the first responders to various stressors that challenge the homeostasis of cells and organisms. Mitochondrial decay is generally associated with impairment in the organelle bioenergetics function and increased oxidative stress, and it appears that deterioration of mitochondrial inner membrane phospholipids (PL), particularly cardiolipin (CL), and accumulation of mitochondrial DNA (mtDNA) mutations are among the main mechanisms involved in this process. In the present study, liver mitochondrial membrane PL compositions, lipid peroxidation, and mtDNA gene expression were analyzed in rainbow trout fed three diets with the same base formulation but with lipid supplied either by fish oil (FO), rapeseed oil (RO), or high DHA oil (DHA) during 6 weeks. Specifically, two feeding trials were performed using fish from the same population of two ages (1 and 3 years), and PL class compositions of liver mitochondria, fatty acid composition of individual PL classes, TBARS content, and mtDNA expression were determined. Dietary fatty acid composition strongly affected mitochondrial membrane composition from trout liver but observed changes did not fully reflect the diet, particularly when it contained high DHA. The changes were PL specific, CL being particularly resistant to changes in DHA. Some significant differences observed in expression of mtDNA with diet may suggest long-term dietary effects in mitochondrial gene expression which could affect electron transport chain function. All the changes were influenced by fish age, which could be related to the different growth rates observed between 1- and 3-year-old trout but that could also indicate age-related changes in the ability to maintain structural homeostasis of mitochondrial membranes.
Open Access
Different patterns of apoptosis in response to cisplatin in B50 neuroblastoma rat cells
(F. Hernández y Juan F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Santin, G.; Piccolini, V.M.; Veneroni, P.; Barni, Sergio; Bernocchi, G.; Bottone, M.G.
Cisplatin (cisPt) is a chemotherapeutic drug used for several human malignancies. CisPt cytotoxicity is primarily mediated by its ability to cause DNA damage and subsequent apoptotic cell death. DNA is the primary target of cisPt; however, recent data have shown that cisPt may have important direct interactions with mitochondria, which can induce apoptosis and may account for a significant part of the clinical activity associated with this drug. We have previously demonstrated that in the rat neuronal cell line B50, at 20 h-treatment with cisPt activates apoptosis through an intrinsic pathway involving an alteration of mitochondrial membrane permeability and the release of cytochrome c. The present study investigates different death pathways induced in the same cell line by a prolonged treatment with 40 µM cisPt for 48 h. To address this issue, we focused on caspases-8 and -12, and on the mitochondrial apoptosis inducing factor (AIF), which translocates to the nucleus and induces cell death via caspase-independent pathway. We found that cisPt activates different forms of cell death, i.e. the receptor-mediated apoptotic extrinsic pathway and a death process mediated by endoplasmic reticulum stress. Moreover, we demonstrated that AIF-mediated death occurs, being characterized by the translocation of AIF from mitochondria to the nucleus. On the whole, we provided evidence that prolonged cisPt treatment is able to activate both caspase-dependent and caspaseindependent apoptotic pathways in B50 rat neuronal cells.
Open Access
Dynamin-related protein 1 (Drp1) mediating mitophagy contributes to the pathophysiology of nervous system diseases and brain injury
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Wu, Qiong; Luo, Cheng Liang; Tao, Lu Yang
As the main source of energy (celluar ATP) in eukaryotic cells, mitochondria are involved in cellular physiology and pathology. The balance of mitochondrial dynamic, fission and fusion regulated by quality control mechanisms, provides a guarantee for maintaining mitochondrial function, even celluar function. Worn out mitochondria would be removed through mitophagy which is regulated by autophagy related proteins and mitochondrial membrane proteins. Drp1, dynamicrelated protein 1, is regarded as one of the most important proteins to evaluate mitochondrial fission mediating mitophagy in neurodegenerative diseases (eg. Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis) and heart failure. Recent studies have focused on the roles of Drp1 in ischemia-induced mitophagy in the hippocampal CA3 region, and traumatic brain injury (TBI)-induced cell death together with functional deficits. However, the exact mechanisms have not been well characterized. In this review, we will discuss and clarify the role of Drp1 and mitophagy in nervous system diseases and brain injury therein, with a special emphasis on their molecular mechanisms mediating mitochondrial dynamics and mitophagy
Open Access
Effects of dietary fatty acids on mitochondrial phospholipid compositions, oxidative status and mitochondrial gene expression of zebrafish at different ages
(Springer, 2015-07-09) Betancor, M B; Almaida Pagán, Pedro Francisco; Hernandez, A; Tocher, D R; Fisiología
Mitochondrial decay is generally associated with impairment in the organelle ioenergetics function and increased oxidative stress, and it appears that deterioration of mitochondrial inner membrane phospholipids (PL) and accumulation of mitochondrial DNA (mtDNA) mutations are among the main mechanisms involved in this process. In the present study, mitochondrial membrane PL compositions, oxidative status (TBARS content and SOD activity) and mtDNA gene expression of muscle and liver were analyzed in zebrafish fed two diets with lipid supplied either by rapeseed oil (RO) or a blend 60:40 of RO and DHA500 TG oil (DHA). Two feeding trials were performed using zebrafish from the same population of two ages (8 and 21 months). Dietary FA composition affected fish growth in 8-month-old animals, which could be related to an increase in stress promoted by diet composition. Lipid peroxidation was considerably higher in mitochondria of 8-month-old zebrafish fed the DHA diet than in animals fed the RO diet. This could indicate higher oxidative damage to mitochondrial lipids, very likely due to increased incorporation of DHA in PL of mitochondrial membranes. Lipids would be among the first molecules affected by mitochondrial reactive oxygen species, and lipid peroxidation could propagate oxidative reactions that would damage other molecules, including mtDNA. Mitochondrial lipid peroxidation and gene expression of 21-month-old fish showed lower responsiveness to diet composition than those of younger fish. Differences found in the effect of diet composition on mitochondrial lipids between the two age groups could be indicating age-related changes in the ability to maintain structural homeostasis of mitochondrial membranes.
Open Access
Endothelial cell activation mediated by cold ischemia-released mitochondria is partially inhibited by defibrotide and impacts on early allograft function following liver transplantation
(Elsevier, 2023-09-18) Villalba-Lopez, Francisco; Mateo, Sandra V.; Vidal-Correoso, Daniel; Jover-Aguilar, Marta; Alconchel, Felipe; Martínez-Alarcón, Laura; López-López, Víctor; Rios-Zambudio, Antonio; Cascales, Pedro; Pons Miñano, José Antonio; Ramírez, Pablo; Baroja-Mazo, Alberto; García Bernal, David; Pelegrín Vivancos, Pablo; Medicina
DAMPs (danger-associated molecular patterns) are self-molecules of the organism that appear after damage. The endothelium plays several roles in organ rejection, such as presenting alloantigens to T cells and contributing to the development of inflammation and thrombosis. This study aimed to assess whether DAMPs present in the organ preservation solution (OPS) after cold ischemic storage (CIS) contribute to exacerbating the endothelial response to an inflammatory challenge and whether defibrotide treatment could counteract this effect. The activation of cultured human umbilical vein endothelial cells (HUVECs) was analyzed after challenging with endischemic OPS (eiOPS) obtained after CIS. Additionally, transwell assays were performed to study the ability of eiOPS to attract lymphocytes across the endothelium. The study revealed that eiOPS upregulated the expression of MCP-1 and IL-6 in HUVECs. Moreover, eiOPS increased the membrane expression of ICAM-1and HLA-DR, which facilitated leukocyte migration toward a chemokine gradient. Furthermore, eiOPS demonstrated its chemoattractant ability. This activation was mediated by free mitochondria. Defibrotide was found to partially inhibit the eiOPS-mediated activation. Moreover, the eiOPS-mediated activation of endothelial cells (ECs) correlated with early allograft dysfunction in liver transplant patients. Our finding provide support for the hypothesis that mitochondria released during cold ischemia could trigger EC activation, leading to complications in graft outcomes. Therefore, the analysis and quantification of free mitochondria in the eiOPS samples obtained after CIS could provide a predictive value for monitoring the progression of transplantation. Moreover, defibrotide emerges as a promising therapeutic agent to mitigate the damage induced by ischemia in donated organs.
Open Access
Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis
(Wiley, 2021-08) Torre-Minguela, Carlos de; Gomez, Ana I.; Couillin, Isabelle; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
Pyroptosis and intrinsic apoptosis are two forms of regulated cell death driven by active caspases where plasma membrane permeabilization is induced by gasdermin pores. Caspase-1 induces gasdermin D pore formation during pyroptosis whereas caspase-3 promotes gasdermin E pore formation during apoptosis. These two types of cell death are accompanied by mitochondrial outer membrane permeabilization due to BAK/BAX pore formation in the external membrane of mitochondria, and to some extent this complex also affects the inner mitochondrial membrane facilitating mitochondrial DNA relocalisation from the matrix to the cytosol. However, the detailed mechanism responsible for this process has not been investigated. Herein, we reported that gasdermin processing is required to induce mitochondrial DNA release from cells during pyroptosis and apoptosis. Gasdermin targeted at the plasma membrane promotes a fast mitochondrial collapse along with the initial accumulation of mitochondrial DNA in the cytosol and then facilitates the DNA’s release from the cell when the plasma membrane ruptures. These findings demonstrate that gasdermin action has a critical effect on the plasma membrane and facilitates the release of mitochondrial DNA as a damage-associated molecular pattern.
Open Access
Heart mitochondria in rats submitted to chronic hypoxia
(Murcia : F. Hernández, 1999) Cervós-Navarro, J.; Kunas, R.Ch.; Sampaolo, S.; Mansmann, U.
The effect of prolonged exposure to normobaric hypoxia on the mitochondria of myocard of rats exposed for several weeks to 8 and 7% O2 has been morphometrically evaluated. Twelve male Wistar rats housed in Nalgene cages (2 per cage) with a batch of six cages placed in plexiglass chambers were maintained in air/N2 mixtures containing different concentrations of 02. Six animals kept in similar cages under normoxia served as controls. When at day 60 the FIOZ was reduced to 8%, the weight increase stagnated and after the 81st test day, on which the hypoxic animals were subdivided into 8% and 7% groups the weight curve showed a decrease in the mean body weight for both groups. The arrest and the following loss of weight beyond the 85th day may be interpreted as the expression of a limit reached in the compensation capacity. In the 8%-group the shape of the mitochondria varied more markedly often with budding and furrowing of the surface. In the 7%-group bizarre shapes and wide variations in size with a decided shift towards larger mitochondria were noteworthy. While rats kept under 8% oxygen exhibited a numerical increase in myocardial mitochondria compared to controls, the mitochondria of the 7%-group were numerically reduced. The results suggest that hypoxia of 8% oxygen is compensatable, if only to some extent, by an increasing surface of mitochondrial membranes, and that further reduction of oxygen causes compensation mechanisms to fail as seen by the severe alterations of the mitochondrial population of the cardiomyocyte in the 7%-group.
Open Access
High-energy adhering junctional complexes or with mitochondrial coupling
(Murcia : F. Hernández, 1987) González Santander, R.; Martínez Cuadrado, G.; Rubio Sáez, M.
A variety of adhering junction is found in the ependyma of the domestic cat with a coupling of mitochondria. These are symmetrically situated (in mirror form) at both sides of the intercellular cleft, which always maintain the same separating distance, thereby leaving a limiting cellular space of a constant amplitude. The hypothesis is put forward that the energy (ATP), provided by the mitochondria over adhering junctional complexes, would produce separate fields of force which would position in a lengthwise direction the molecules which give rise to the anchoring filaments. The mitochondrial energy provided and the electrostatic forces generated would produce an adhering, intercellular junction which is functionally very strong and which could be called: high-energy adhering junctional complexes or with mitochondrial coupling.
Open Access
Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) García, Sebastián; Martín Giménez, Virna Margarita; Mocayar Marón, Feres José; Reiter, Russel J.; Manucha, Walter
Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of "neuroinflammaging" has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging. Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuro- inflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson's and Alzheimer's diseases. Some of these neuroprotective effects are fundamentally related to its anti- inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland.
Open Access
Melatonin protects against sarcopenia in middle-aged mice
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Fang, Fei; Yu, Ping; Sun, Xiaoying; Shen, Zhixing; Zhang, Fan; Sun, Jianwei
Background. Sarcopenia is a common age-related disease. Melatonin (MEL) is an age-related endocrine hormone, which displays a crucial role in resisting oxidative stress during aging. Importantly, the antioxidant properties of MEL can be mediated by mitochondria. Objective. Therefore, we wondered whether MEL could mitigate oxidative stress caused by mitochondria in sarcopenia. Methods. The middle-aged mice were administered 5 mg/kg/d and 10 mg/kg/d of MEL for 2 months. Young mice were used as the control group. Results. After treatment with MEL, the grip strength of the fore/hind limbs, running time, and distance were elevated, and the weights of the gastrocnemius (GA), tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) were enhanced in middle-aged mice. Additionally, MEL was observed to alleviate histological damage and increase the cross-sectional area of muscle fibers in GA tissues of middle-aged mice. Furthermore, following MEL treatment, there was an increase in the percentage and size of normal mitochondria as well as mtDNA copy number but a reduction in the levels of malondialdehyde (MDA), protein carbonyl, and reactive oxygen species (ROS) in the GA tissues of middle-aged mice. At the molecular level, MEL repressed the levels of ATROGIN-1, muscle RING-finger protein-1 (MURF-1), and the ratio of p-P38/P38, but elevated the expression of cytochrome c oxidase subunit 4 (COX4), cystatin C (CYTC), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in the GA tissues of middle-aged mice. Importantly, 10 mg/kg MEL was more efficacious in the treatment of sarcopenia than 5 mg/kg MEL. Conclusion. MEL attenuates sarcopenia in middle-aged mice, and the mechanism may relate to mitochondria-induced oxidative stress and the PGC-1α/TFAM pathway
Open Access
Mitochondrial cholesterol in health and disease
(Murcia : F. Hernández, 2009) Garcia-Ruiz, Carmen; Mari, Monserrat; Colell, Ana; Morales, Albert; Caballero, Francisco; Montero, Joan; Terrones, Ohiana; Basañez, Gorka; Fernández-Checa, José C.
Cholesterol is a critical component of biological membranes, which not only plays an essential role in determining membrane physical properties, but also in the regulation of multiple signaling pathways. Cells satisfy their need for cholesterol either by uptake from nutrients and lipoproteins or de novo synthesis from acetyl-CoA. The latter process occurs in the endoplasmic reticulum, where transcription factors that regulate the expression of enzymes involved in the de novo cholesterol synthesis reside. Cholesterol is distributed to different membranes most prominently to plasma membrane, where it participates in the physical organization of specific membrane domains. Mitochondria, however, are considered cholesterol-poor organelles, and obtain their cholesterol load by the action of specialized proteins involved in its delivery from extramitochondrial sources and trafficking within mitochondrial membranes. Although mitochondrial cholesterol fulfills vital physiological functions, such as the synthesis of bile acids in the liver or the formation of steroid hormones in specialized tissues, recent evidence indicates that the accumulation of cholesterol in mitochondria may be a key step in disease progression, including steatohepatitis, carcinogenesis or Alzheimer disease.
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Mitochondrial damage as death inducer in heart-derived H9c2 cells: more than one way for an early demise
(Springer, 2009-09-24) Lax Pérez, Antonio Manuel; Fernandez Belda, Francisco; Soler Pardo, Fernando; Medicina
The release of cytochrome c from mitochondria induced by 10 microM thapsigargin was linked to rapid loss of the mitochondrial membrane potential whereas that induced by 50 nM staurosporine was mediated by Bax activation and occurred in polarized mitochondria. Similar levels of cytochrome c were observed when induced by either thapsigargin or staurosporine indicating that the release magnitude was independent of the mechanism involved in membrane permeabilization. In any case caspase 3 activation was subsequent to cytochrome c release. Mitochondrial dysfunction and release of cytochrome c occurred earlier when induced by thapsigargin even though morphological alteration of the cell and chromatin condensation were developed earlier in the presence of staurosporine. In addition, a general and irreversible caspase inhibitor did not protect against chromatin condensation induced by staurosporine. It is also shown that earlier mitochondrial damage does not always correlate with earlier cell demise. This can be attributed to the existence of alternative caspase-independent cell death programmes.