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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 -
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 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 -
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 -
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 -
Mitochondrion Jan 2020Mitochondrial function relies on the activity of oxidative phosphorylation to synthesise ATP and generate an electrochemical gradient across the inner mitochondrial... (Review)
Review
Mitochondrial function relies on the activity of oxidative phosphorylation to synthesise ATP and generate an electrochemical gradient across the inner mitochondrial membrane. These coupled processes are mediated by five multi-subunit complexes that reside in this inner membrane. These complexes are the product of both nuclear and mitochondrial gene products. Defects in the function or assembly of these complexes can lead to mitochondrial diseases due to deficits in energy production and mitochondrial functions. Appropriate biogenesis and function are mediated by a complex number of assembly factors that promote maturation of specific complex subunits to form the active oxidative phosphorylation complex. The understanding of the biogenesis of each complex has been informed by studies in both simple eukaryotes such as Saccharomyces cerevisiae and human patients with mitochondrial diseases. These studies reveal each complex assembles through a pathway using specific subunits and assembly factors to form kinetically distinct but related assembly modules. The current understanding of these complexes has embraced the revolutions in genomics and proteomics to further our knowledge on the impact of mitochondrial biology in genetics, medicine, and evolution.
Topics: Animals; Electron Transport Chain Complex Proteins; Electron Transport Complex IV; Gene Expression Regulation, Enzymologic; Mammals; Mitochondria; Yeasts
PubMed: 31669617
DOI: 10.1016/j.mito.2019.10.008 -
Mitochondrion Nov 2023Allotopic expression is the functional transfer of an organellar gene to the nucleus, followed by synthesis of the gene product in the cytosol and import into the... (Review)
Review
Allotopic expression is the functional transfer of an organellar gene to the nucleus, followed by synthesis of the gene product in the cytosol and import into the appropriate organellar sub compartment. Here, we focus on mitochondrial genes encoding OXPHOS subunits that were naturally transferred to the nucleus, and critically review experimental evidence that claim their allotopic expression. We emphasize aspects that may have been overlooked before, i.e., when modifying a mitochondrial gene for allotopic expression━besides adapting the codon usage and including sequences encoding mitochondrial targeting signals━three additional constraints should be considered: (i) the average apparent free energy of membrane insertion (μΔG) of the transmembrane stretches (TMS) in proteins earmarked for the inner mitochondrial membrane, (ii) the final, functional topology attained by each membrane-bound OXPHOS subunit; and (iii) the defined mechanism by which the protein translocator TIM23 sorts cytosol-synthesized precursors. The mechanistic constraints imposed by TIM23 dictate the operation of two pathways through which alpha-helices in TMS are sorted, that eventually determine the final topology of membrane proteins. We used the biological hydrophobicity scale to assign an average apparent free energy of membrane insertion (μΔG) and a "traffic light" color code to all TMS of OXPHOS membrane proteins, thereby predicting which are more likely to be internalized into mitochondria if allotopically produced. We propose that the design of proteins for allotopic expression must make allowance for μΔG maximization of highly hydrophobic TMS in polypeptides whose corresponding genes have not been transferred to the nucleus in some organisms.
Topics: Mitochondria; Mitochondrial Membranes; Membrane Proteins; Genes, Mitochondrial; Protein Transport; Saccharomyces cerevisiae Proteins
PubMed: 37739243
DOI: 10.1016/j.mito.2023.09.004 -
Mitochondrion May 2017There is an extraordinary diversity of reproductive modes in teleost and this variability is related to the phylogenetic relationships and adaption to very different... (Review)
Review
There is an extraordinary diversity of reproductive modes in teleost and this variability is related to the phylogenetic relationships and adaption to very different biotopes. As in all vertebrates, sperm is produced as the end product of the process of spermatogenesis, and regarding teleost the spermatozoa lack an acrosome in almost all species and motility is activated as a response to osmolarity and ion content of the aquatic medium where the sperm is released. In this context, mitochondria possess a fundamental role for fish spermatozoa motility and integrity, hence, fertilizing potential; they are the energy supplier that allows flagellar movement and their dysfunction could play a main role in structural and functional damage to the spermatozoa. The ATP production through oxidative phosphorylation provides not only energy for cell activities, which includes Na/K ATPase pump, endocytosis, protein synthesis and many other cell processes; but also produces reactive oxygen species, that under mitochondrial dysfunction causes oxidative stress. The assessment of mitochondrial function (e.g. through measurement of mitochondrial membrane potential) as well as ATP content (mostly supplied by mitochondrial respiration) can be useful as quality markers of fish spermatozoa. Also quantification of ROS and antioxidant status, strongly influenced by mitochondria, are used as complementary measurements. There is much information about sperm mitochondria and their function but studies of these aspects on fish reproduction are still required for applications in aquaculture. The real role of fish sperm mitochondria under short and long term storage and in vitro manipulation is not fully understood yet. Thus future research should focus on these matters.
Topics: Animals; Cell Movement; Energy Metabolism; Fishes; Male; Mitochondria; Reactive Oxygen Species; Spermatozoa
PubMed: 28065674
DOI: 10.1016/j.mito.2017.01.001 -
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