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Journal of Biochemical and Molecular... Nov 2021Maintenance of mitochondrial oxidative phosphorylation capacity and other mitochondrial functions are essential for the prevention of mitochondrial dysfunction-related... (Review)
Review
Maintenance of mitochondrial oxidative phosphorylation capacity and other mitochondrial functions are essential for the prevention of mitochondrial dysfunction-related diseases such as neurodegenerative, cardiovascular, and liver diseases. To date, no well-known treatment modality has been developed to prevent or reduce mitochondrial dysfunction. However, a novel approach that transplants fully functional mitochondria directly into defective cells has recently caught the attention of scientists. In this review, we provide an overview of the cell/tissue source of the mitochondria to prompt cell regeneration or tissue repair in vitro and in vivo applications. The animal and human models entail that effective procedures should be used in the isolation and confirmation of mitochondrial membrane potential and function. We believe that these procedures for mitochondrial transplantation for tissue or cell culture will confirm intact, viable, and free from contamination isolated mitochondria from the appropriate sources.
Topics: Animals; Humans; Mitochondria; Oxidative Phosphorylation
PubMed: 34435410
DOI: 10.1002/jbt.22898 -
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 -
Mitochondrion Mar 2023This article intends to provide an update of the needs in the field working in the artificial mitochondrial transfer/transplant (AMT/T), and an overview of the...
This article intends to provide an update of the needs in the field working in the artificial mitochondrial transfer/transplant (AMT/T), and an overview of the highlights from the articles in the special issue "Advances of Mitochondria as a therapeutic agent". In the last 4 decades, scientists have developed innovative therapeutic applications based on the AMT/T, inspired by the natural transfer of mitochondria between cells to repair cellular damage or treat diseases. The clinical application of AMT has become the priority for the field involving the replacement or augmentation of healthy mitochondria in the harmed tissue, especially in the treatment of organ ischemia-reperfusion injury. However, we remark in our article that key questions remain to be answered such as which one is the best isolation protocol, tissue or cell source for isolation, and others of great importance to move the field forward.
Topics: Humans; Mitochondria; Reperfusion Injury
PubMed: 36657505
DOI: 10.1016/j.mito.2023.01.003 -
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 -
Current Medicinal Chemistry 2021Mitochondria are a potent source of cellular reactive oxygen species (ROS) and are vulnerable to oxidative damage. Mitochondria dysfunction could result in adenosine... (Review)
Review
Mitochondria are a potent source of cellular reactive oxygen species (ROS) and are vulnerable to oxidative damage. Mitochondria dysfunction could result in adenosine triphosphate (ATP) decrease and cell death. The kidney is an ATP-consuming organ, and the relationship between mitochondrial dysfunction and renal disease has been long noted. Mitochondrial targeting is a novel strategy for kidney diseases. At present, there are several ways to target mitochondria, such as the addition of a triphenylphosphonium cation, mitochondria-targeted peptides, and nanocarrier. There are also a variety of choices for the payload, such as nitroxides, quinone derivates, vitamins and so on. This review summarized the chemical and also clinical characteristics of various mitochondria- targeted antioxidants and focused on their application and perspectives in kidney diseases.
Topics: Antioxidants; Humans; Kidney Diseases; Mitochondria; Oxidative Stress; Reactive Oxygen Species
PubMed: 33081669
DOI: 10.2174/0929867327666201020151124 -
Mitochondrion Jul 2020Plant mitochondria operate as the powerhouses for cellular energy production by using the combined functions of both imported and organelle-synthesised proteins.... (Review)
Review
Plant mitochondria operate as the powerhouses for cellular energy production by using the combined functions of both imported and organelle-synthesised proteins. Homeostasis of mitochondrial proteins is controlled by both synthesis and degradation processes which together define protein turnover in this organelle. Better understanding of plant mitochondrial protein turnover will provide information on protein quality control inside these organelles and its importance for proper function and regulation of mitochondrial machinery. This review discusses methods used for measurement of turnover rates of plant mitochondrial proteins and presents our current understanding of these rates for key mitochondrial proteins and protein complexes. The assembly and maintenance of mitochondrial OXPHOS complexes, in particular Complexes I and V, will be discussed in detail based on the evidence for differential protein turnover rates of the same protein subunits in different mitochondrial fractions. The impact of the loss of specific plant mitochondrial proteases on proteolysis events and rates of mitochondrial protein turnover will be highlighted. The challenges and future directions for investigation of plant mitochondrial protein turnover are also discussed.
Topics: Homeostasis; Mitochondria; Mitochondrial Proteins; Oxidative Phosphorylation; Plant Proteins; Plants; Proteolysis
PubMed: 32387507
DOI: 10.1016/j.mito.2020.04.011 -
Mitochondrion Jul 2021Sepsis is a systemic inflammatory disease with an unacceptably high mortality rate caused by an infection or trauma that involves both innate and adaptive immune... (Review)
Review
Sepsis is a systemic inflammatory disease with an unacceptably high mortality rate caused by an infection or trauma that involves both innate and adaptive immune systems. Inflammatory events activate different downstream pathways leading to tissue damage and ultimately multi-organ failure. Mitochondria are responsible for cellular energy, thermoregulation, metabolite biosynthesis, intracellular calcium regulation, and cell death. Damaged mitochondria induce the high Ca influx through mitochondrial calcium uniporter (MCU). It also generates excessive Reactive oxygen species (ROS) and releases mtDNA into the cytoplasm, which causes induction of NLRP3 inflammasome and apoptosis. Mitophagy (Autophagy of damaged mitochondria) controls mitochondrial dynamics and function. It also maintains cellular homeostasis. This review is about how pulmonary sepsis affects the body. What is the aftermath of sepsis, and how mitophagy affects Acute Lung Injury and macrophage polarisation to overcome the damages.
Topics: Calcium; Calcium Channels; DNA, Mitochondrial; Humans; Inflammasomes; Mitochondria; Mitochondrial Dynamics; Mitophagy; Pneumonia; Sepsis
PubMed: 33894359
DOI: 10.1016/j.mito.2021.04.009 -
Mitochondrion May 2022Mitochondrial transplantation involves the replacement or augmentation of native mitochondria damaged, by ischemia, with viable, respiration-competent mitochondria... (Review)
Review
Mitochondrial transplantation involves the replacement or augmentation of native mitochondria damaged, by ischemia, with viable, respiration-competent mitochondria isolated from non-ischemic tissue obtained from the patient's own body. The uptake and cellular functional integration of the transplanted mitochondria appears to occur in all cell types. Efficacy and safety have been demonstrated in cell culture, isolated perfused organ, in vivo large animal studies and in a first-human clinical study. Herein, we review our findings and provide insight for use in the treatment of organ ischemia- reperfusion injury.
Topics: Animals; Cell Culture Techniques; Mitochondria; Mitochondria, Heart; Reperfusion Injury
PubMed: 35217248
DOI: 10.1016/j.mito.2022.02.007 -
Journal of Periodontal Research Oct 2023Periodontitis is an inflammatory and destructive disease of tooth-supporting tissue and has become the leading cause of adult tooth loss. The most central pathological... (Review)
Review
Periodontitis is an inflammatory and destructive disease of tooth-supporting tissue and has become the leading cause of adult tooth loss. The most central pathological features of periodontitis are tissue damage and inflammatory reaction. As the energy metabolism center of eukaryotic cells, mitochondrion plays a notable role in various processes, such as cell function and inflammatory response. When the intracellular homeostasis of mitochondrion is disrupted, it can lead to mitochondrial dysfunction and inability to generate adequate energy to maintain basic cellular biochemical reactions. Recent studies have revealed that mitochondrial dysfunction is closely related to the initiation and development of periodontitis. The excessive production of mitochondrial reactive oxygen species, imbalance of mitochondrial biogenesis and dynamics, mitophagy and mitochondrial DNA damage can all affect the development and progression of periodontitis. Thus, targeted mitochondrial therapy is potentially promising in periodontitis treatment. In this review, we summarize the above mitochondrial mechanism in the pathogenesis of periodontitis and discuss some potential approaches that can exert therapeutic effects on periodontitis by modulating mitochondrial activity. The understanding and summary of mitochondrial dysfunction in periodontitis might provide new research directions for pathological intervention or treatment of periodontitis.
Topics: Adult; Humans; Oxidative Stress; Mitochondria; Reactive Oxygen Species; DNA, Mitochondrial; Periodontitis
PubMed: 37332252
DOI: 10.1111/jre.13152