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Nutrition Reviews Jan 2021Mitochondrial dysfunction is observed in a broad range of human diseases, including rare genetic disorders and complex acquired pathologies. For this reason, there is... (Review)
Review
Mitochondrial dysfunction is observed in a broad range of human diseases, including rare genetic disorders and complex acquired pathologies. For this reason, there is increasing interest in identifying safe and effective strategies to mitigate mitochondrial impairments. Natural compounds are widely used for multiple indications, and their broad healing properties suggest that several may improve mitochondrial function. This review focuses on (-)-epicatechin, a monomeric flavanol, and its effects on mitochondria. The review summarizes the available data on the effects of acute and chronic (-)-epicatechin supplementation on mitochondrial function, outlines the potential mechanisms involved in mitochondrial biogenesis induced by (-)-epicatechin supplementation and discusses some future therapeutic applications.
Topics: Animals; Biological Availability; Catechin; Humans; Mitochondria
PubMed: 32989466
DOI: 10.1093/nutrit/nuaa094 -
Biochimica Et Biophysica Acta.... Feb 2021The mitochondrion is often referred as the cellular powerhouse because the organelle oxidizes organic acids and NADH derived from nutriments, converting around 40% of... (Review)
Review
The mitochondrion is often referred as the cellular powerhouse because the organelle oxidizes organic acids and NADH derived from nutriments, converting around 40% of the Gibbs free energy change of these reactions into ATP, the major energy currency of cell metabolism. Mitochondria are thus microscopic furnaces that inevitably release heat as a by-product of these reactions, and this contributes to body warming, especially in endotherms like birds and mammals. Over the last decade, the idea has emerged that mitochondria could be warmer than the cytosol, because of their intense energy metabolism. It has even been suggested that our own mitochondria could operate under normal conditions at a temperature close to 50 °C, something difficult to reconcile with the laws of thermal physics. Here, using our combined expertise in biology and physics, we exhaustively review the reports that led to the concept of a hot mitochondrion, which is essentially based on the development and use of a variety of molecular thermosensors whose intrinsic fluorescence is modified by temperature. Then, we discuss the physical concepts of heat diffusion, including mechanisms like phonons scattering, which occur in the nanoscale range. Although most of approaches with thermosensors studies present relatively sparse data and lack absolute temperature calibration, overall, they do support the hypothesis of hot mitochondria. However, there is no convincing physical explanation that would allow the organelle to maintain a higher temperature than its surroundings. We nevertheless proposed some research directions, mainly biological, that might help throw light on this intriguing conundrum.
Topics: Animals; Energy Metabolism; Humans; Mitochondria
PubMed: 33248118
DOI: 10.1016/j.bbabio.2020.148348 -
Mitochondrion Nov 2019Spatiotemporal changes in the abundance, shape, and cellular localization of the mitochondrial network, also known as mitochondrial dynamics, are now widely recognized... (Review)
Review
Spatiotemporal changes in the abundance, shape, and cellular localization of the mitochondrial network, also known as mitochondrial dynamics, are now widely recognized to play a key role in mitochondrial and cellular physiology as well as disease states. This process involves coordinated remodeling of the outer and inner mitochondrial membranes by conserved dynamin-like guanosine triphosphatases and their partner molecules in response to various physiological and stress stimuli. Although the core machineries that mediate fusion and partitioning of the mitochondrial network have been extensively characterized, many aspects of their function and regulation are incompletely understood and only beginning to emerge. In the present review we briefly summarize current knowledge about how the key mitochondrial dynamics-mediating factors are regulated via selective proteolysis by mitochondrial and cellular proteolytic machineries.
Topics: Animals; Mitochondria; Mitochondrial Dynamics; Mitochondrial Membranes; Mitochondrial Proteins; Proteolysis
PubMed: 31029640
DOI: 10.1016/j.mito.2019.04.008 -
Journal of Biochemistry Mar 2020The mitochondrion is an essential organelle for a wide range of cellular processes, including energy production, metabolism, signal transduction and cell death. To... (Review)
Review
The mitochondrion is an essential organelle for a wide range of cellular processes, including energy production, metabolism, signal transduction and cell death. To execute these functions, mitochondria regulate their size, number, morphology and distribution in cells via mitochondrial division and fusion. In addition, mitochondrial division and fusion control the autophagic degradation of dysfunctional mitochondria to maintain a healthy population. Defects in these dynamic membrane processes are linked to many human diseases that include metabolic syndrome, myopathy and neurodegenerative disorders. In the last several years, our fundamental understanding of mitochondrial fusion, division and degradation has been significantly advanced by high resolution structural analyses, protein-lipid biochemistry, super resolution microscopy and in vivo analyses using animal models. Here, we summarize and discuss this exciting recent progress in the mechanism and function of mitochondrial division and fusion.
Topics: Actins; Animals; Dynamins; Endoplasmic Reticulum; GTP Phosphohydrolases; Humans; Lipid Metabolism; Mitochondria; Mitochondrial Dynamics; Mitophagy
PubMed: 31800050
DOI: 10.1093/jb/mvz106 -
Viruses Dec 2023Mitochondria have been identified as the "powerhouse" of the cell, generating the cellular energy, ATP, for almost seven decades. Research over time has uncovered a... (Review)
Review
Mitochondria have been identified as the "powerhouse" of the cell, generating the cellular energy, ATP, for almost seven decades. Research over time has uncovered a multifaceted role of the mitochondrion in processes such as cellular stress signaling, generating precursor molecules, immune response, and apoptosis to name a few. Dysfunctional mitochondria resulting from a departure in homeostasis results in cellular degeneration. Viruses hijack host cell machinery to facilitate their own replication in the absence of a bonafide replication machinery. Replication being an energy intensive process necessitates regulation of the host cell oxidative phosphorylation occurring at the electron transport chain in the mitochondria to generate energy. Mitochondria, therefore, can be an attractive therapeutic target by limiting energy for viral replication. In this review we focus on the physiology of oxidative phosphorylation and on the limited studies highlighting the regulatory effects viruses induce on the electron transport chain.
Topics: Humans; Oxidative Phosphorylation; Mitochondria; Apoptosis; Signal Transduction; Virus Diseases; Phosphorylation; Oxidative Stress
PubMed: 38140621
DOI: 10.3390/v15122380 -
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 -
International Journal of Molecular... Oct 2020Mitochondrial dysfunction is associated with ageing, but the detailed causal relationship between the two is still unclear. We review the major phenomenological... (Review)
Review
Mitochondrial dysfunction is associated with ageing, but the detailed causal relationship between the two is still unclear. We review the major phenomenological manifestations of mitochondrial age-related dysfunction including biochemical, regulatory and energetic features. We conclude that the complexity of these processes and their inter-relationships are still not fully understood and at this point it seems unlikely that a single linear cause and effect relationship between any specific aspect of mitochondrial biology and ageing can be established in either direction.
Topics: Animals; Cellular Senescence; Genome, Mitochondrial; Humans; Mitochondria; Organelle Biogenesis
PubMed: 33066461
DOI: 10.3390/ijms21207580 -
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 -
Journal of Internal Medicine Jun 2020Mitochondrial diseases are extremely heterogeneous genetic conditions characterized by faulty oxidative phosphorylation (OXPHOS). OXPHOS deficiency can be the result of... (Review)
Review
Mitochondrial diseases are extremely heterogeneous genetic conditions characterized by faulty oxidative phosphorylation (OXPHOS). OXPHOS deficiency can be the result of mutation in mtDNA genes, encoding either proteins (13 subunits of the mitochondrial complexes I, III, IV and V) or the tRNA and rRNA components of the in situ mtDNA translation. The remaining mitochondrial disease genes are in the nucleus, encoding proteins with a huge variety of functions, from structural subunits of the mitochondrial complexes, to factors involved in their formation and regulation, components of the mtDNA replication and expression machinery, biosynthetic enzymes for the biosynthesis or incorporation of prosthetic groups, components of the mitochondrial quality control and proteostasis, enzymes involved in the clearance of toxic compounds, factors involved in the formation of the lipid milieu, etc. These different functions represent potential targets for 'general' therapeutic interventions, as they may be adapted to a number of different mitochondrial conditions. This is in contrast with 'tailored', personalized therapeutic approaches, such as gene therapy, cell therapy and organ replacement, that can be useful only for individual conditions. This review will present the most recent concepts emerged from preclinical work and the attempts to translate them into the clinics. The common notion that mitochondrial disorders have no cure is currently challenged by a massive effort of scientists and clinicians, and we do expect that thanks to this intensive investigation work and tangible results for the development of strategies amenable to the treatment of patients with these tremendously difficult conditions are not so far away.
Topics: Animals; Antioxidants; Genetic Therapy; Humans; Mitochondria; Mitochondrial Diseases; Nucleotides; Translational Research, Biomedical
PubMed: 32100338
DOI: 10.1111/joim.13046