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Cellular and Molecular Life Sciences :... Nov 2017The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis... (Review)
Review
The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis in response to noxious factors. An important part of the skin response to stress is its ability for melatonin synthesis and subsequent metabolism through the indolic and kynuric pathways. Indeed, melatonin and its metabolites have emerged as indispensable for physiological skin functions and for effective protection of a cutaneous homeostasis from hostile environmental factors. Moreover, they attenuate the pathological processes including carcinogenesis and other hyperproliferative/inflammatory conditions. Interestingly, mitochondria appear to be a central hub of melatonin metabolism in the skin cells. Furthermore, substantial evidence has accumulated on the protective role of the melatonin against ultraviolet radiation and the attendant mitochondrial dysfunction. Melatonin and its metabolites appear to have a modulatory impact on mitochondrion redox and bioenergetic homeostasis, as well as the anti-apoptotic effects. Of note, some metabolites exhibit even greater impact than melatonin alone. Herein, we emphasize that melatonin-mitochondria axis would control integumental functions designed to protect local and perhaps global homeostasis. Given the phylogenetic origin and primordial actions of melatonin, we propose that the melatonin-related mitochondrial functions represent an evolutionary conserved mechanism involved in cellular adaptive response to skin injury and repair.
Topics: Animals; Antioxidants; Humans; Melatonin; Mitochondria; Skin; Skin Physiological Phenomena
PubMed: 28803347
DOI: 10.1007/s00018-017-2617-7 -
EMBO Reports Jun 2020Multicellular organisms are complex biological systems, composed of specialized tissues that require coordination of the metabolic and fitness state of each component.... (Review)
Review
Multicellular organisms are complex biological systems, composed of specialized tissues that require coordination of the metabolic and fitness state of each component. In the cells composing the tissues, one central organelle is the mitochondrion, a compartment essential for many energetic and fundamental biological processes. Beyond serving these functions, mitochondria have emerged as signaling hubs in biological systems, capable of inducing changes to the cell they are in, to cells in distal tissues through secreted factors, and to overall animal physiology. Here, we describe our current understanding of these communication mechanisms in the context of mitochondrial stress. We focus on cellular mechanisms that deal with perturbations to the mitochondrial proteome and outline recent advances in understanding how local perturbations can affect distal tissues and animal physiology in model organisms. Finally, we discuss recent findings of these responses associated with metabolic and age-associated diseases in mammalian systems, and how they may be employed as diagnostic and therapeutic tools.
Topics: Animals; Mammals; Mitochondria; Proteome; Signal Transduction
PubMed: 32449292
DOI: 10.15252/embr.202050094 -
Frontiers in Immunology 2023Owing to the complex pathophysiological features and heterogeneity of sepsis, current diagnostic methods are not sufficiently precise or timely, causing a delay in...
BACKGROUND
Owing to the complex pathophysiological features and heterogeneity of sepsis, current diagnostic methods are not sufficiently precise or timely, causing a delay in treatment. It has been suggested that mitochondrial dysfunction plays a critical role in sepsis. However, the role and mechanism of mitochondria-related genes in the diagnostic and immune microenvironment of sepsis have not been sufficiently investigated.
METHODS
Mitochondria-related differentially expressed genes (DEGs) were identified between human sepsis and normal samples from GSE65682 dataset. Least absolute shrinkage and selection operator (LASSO) regression and the Support Vector Machine (SVM) analyses were carried out to locate potential diagnostic biomarkers. Gene ontology and gene set enrichment analyses were conducted to identify the key signaling pathways associated with these biomarker genes. Furthermore, correlation of these genes with the proportion of infiltrating immune cells was estimated using CIBERSORT. The expression and diagnostic value of the diagnostic genes were evaluated using GSE9960 and GSE134347 datasets and septic patients. Furthermore, we established an sepsis model using lipopolysaccharide (1 µg/mL)-stimulated CP-M191 cells. Mitochondrial morphology and function were evaluated in PBMCs from septic patients and CP-M191 cells, respectively.
RESULTS
In this study, 647 mitochondrion-related DEGs were obtained. Machine learning confirmed six critical mitochondrion-related DEGs, including , , , , , and . We then developed a diagnostic model using the six genes, and receiver operating characteristic (ROC) curves indicated that the novel diagnostic model based on the above six critical genes screened sepsis samples from normal samples with area under the curve (AUC) = 1.000, which was further demonstrated in the GSE9960 and GSE134347 datasets and our cohort. Importantly, we also found that the expression of these genes was associated with different kinds of immune cells. In addition, mitochondrial dysfunction was mainly manifested by the promotion of mitochondrial fragmentation (p<0.05), impaired mitochondrial respiration (p<0.05), decreased mitochondrial membrane potential (p<0.05), and increased reactive oxygen species (ROS) generation (p<0.05) in human sepsis and LPS-simulated sepsis models.
CONCLUSION
We constructed a novel diagnostic model containing six MRGs, which has the potential to be an innovative tool for the early diagnosis of sepsis.
Topics: Humans; Mitochondria; DNA, Mitochondrial; Sepsis; Area Under Curve; Gene Ontology; Lipopolysaccharides
PubMed: 37398680
DOI: 10.3389/fimmu.2023.1196306 -
Life Sciences Jun 2023Aging is a natural process, characterized by progressive loss of physiological integrity, impaired function, and increased vulnerability to death. For centuries, people... (Review)
Review
Aging is a natural process, characterized by progressive loss of physiological integrity, impaired function, and increased vulnerability to death. For centuries, people have been trying hard to understand the process of aging and find effective ways to delay it. However, limited breakthroughs have been made in anti-aging area. Since the hallmarks of aging were summarized in 2013, increasing studies focus on the role of mitochondrial dysfunction in aging and aging-related degenerative diseases, such as neurodegenerative diseases, osteoarthritis, metabolic diseases, and cardiovascular diseases. Accumulating evidence indicates that restoring mitochondrial function and biogenesis exerts beneficial effects in extending lifespan and promoting healthy aging. In this paper, we provide an overview of mitochondrial changes during aging and summarize the advanced studies in mitochondrial therapies for the treatment of degenerative diseases. Current challenges and future perspectives are proposed to provide novel and promising directions for future research.
Topics: Humans; Aging; Mitochondria; Cardiovascular Diseases; Signal Transduction; Longevity
PubMed: 37030614
DOI: 10.1016/j.lfs.2023.121666 -
Mitochondrion Jul 2018Mitochondria fulfill important and diverse roles during the different stages of T cell adaptive responses. Here we discuss the role of the mitochondria in T cells from... (Review)
Review
Mitochondria fulfill important and diverse roles during the different stages of T cell adaptive responses. Here we discuss the role of the mitochondria in T cells from the initial steps of activation at the immune synapse to their participation in memory response and T cell exhaustion. Mitochondria are relocated to the immune synapse in order to supply local ATP and to aid calcium signaling. During expansion and proliferation, mitochondrial reactive oxygen species drive proliferation. Aerobic glycolysis, glutaminolysis and fatty acid oxidation regulate the program of differentiation into effector or regulatory T cell subsets, and mitochondrial remodeling proteins are required for the long-lasting phenotype of memory cells.
Topics: Animals; Energy Metabolism; Humans; Immunity, Innate; Metabolic Diseases; Mitochondria; Signal Transduction; T-Lymphocytes
PubMed: 29032101
DOI: 10.1016/j.mito.2017.10.006 -
Schizophrenia Research Sep 2017The prevalence of some mental illnesses, including major depression, anxiety-, trauma-, and stress-related disorders, some substance use disorders, and later onset of... (Review)
Review
The prevalence of some mental illnesses, including major depression, anxiety-, trauma-, and stress-related disorders, some substance use disorders, and later onset of schizophrenia, is higher in women than men. While the higher prevalence in women could simply be explained by socioeconomic determinants, such as income, social status, or cultural background, extensive studies show sex differences in biological, pharmacokinetic, and pharmacological factors contribute to females' vulnerability to these mental illnesses. In this review, we focus on estrogens, chronic stress, and neurotoxicity from behavioral, pharmacological, biological, and molecular perspectives to delineate the sex differences in these mental illnesses. Particularly, we investigate a possible role of mitochondrial function, including biosynthesis, bioenergetics, and signaling, on mediating the sex differences in psychiatric disorders.
Topics: Animals; Humans; Mental Disorders; Mitochondria; Sex Characteristics
PubMed: 28279571
DOI: 10.1016/j.schres.2017.02.025 -
Mitochondrion Mar 2020Autophagy is a ubiquitous homeostatic mechanism for the degradation or turnover of cellular components. Degradation of mitochondria via autophagy (mitophagy) is involved... (Review)
Review
Autophagy is a ubiquitous homeostatic mechanism for the degradation or turnover of cellular components. Degradation of mitochondria via autophagy (mitophagy) is involved in a number of physiological processes including cellular homeostasis, differentiation and aging. Upon stress or injury, mitophagy prevents the accumulation of damaged mitochondria and the increased steady state levels of reactive oxygen species leading to oxidative stress and cell death. A number of human diseases, particularly neurodegenerative disorders, have been linked to the dysregulation of mitophagy. In this mini-review, we aimed to review the molecular mechanisms involved in the regulation of mitophagy and their relationship with redox signaling and oxidative stress.
Topics: Aging; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Dynamics; Mitophagy; Neurodegenerative Diseases; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species
PubMed: 31972372
DOI: 10.1016/j.mito.2020.01.002 -
Mitochondrion Sep 2016Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential functions beyond energy production, impacting most areas... (Review)
Review
Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel mitopathogenic mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article, we overview specific aspects of mitochondrial biology that have contributed to - and likely will continue to enhance the progress of modern medicine.
Topics: Energy Metabolism; Humans; Medicine; Mitochondria; Mitochondrial Diseases
PubMed: 27423788
DOI: 10.1016/j.mito.2016.07.003 -
Cell Calcium Dec 2021
Topics: Mitochondria
PubMed: 34784537
DOI: 10.1016/j.ceca.2021.102498 -
BioMed Research International 2017The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging... (Review)
Review
The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging from metabolism to apoptosis. The mitochondrial-targeted molecular imaging could potentially illustrate changes in global and regional cardiac dysfunction. The collective changes that occur in mitochondrial-targeted molecular imaging probes have been widely explored and developed. As probes currently used in the preclinical setting still have a lot of shortcomings, the development of myocardial metabolic activity, viability, perfusion, and blood flow molecular imaging probes holds great potential for accurately evaluating the myocardial viability and functional reserve. The advantages of molecular imaging provide a perspective on investigating the mitochondrial function of the myocardium in vivo noninvasively and quantitatively. The molecular imaging tracers of single-photon emission computed tomography and positron emission tomography could give more detailed information on myocardial metabolism and restoration. In this study, series mitochondrial-targeted Tc-, I-, and F-labeled tracers displayed broad applications because they could provide a direct link between mitochondrial dysfunction and cardiac disease.
Topics: Animals; Heart Diseases; Humans; Mitochondria, Heart; Molecular Imaging; Radiopharmaceuticals
PubMed: 28638829
DOI: 10.1155/2017/5246853