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Frontiers in Immunology 2024Metabolism and immunity are crucial monitors of the whole-body homeodynamics. All cells require energy to perform their basic functions. One of the most important... (Review)
Review
Metabolism and immunity are crucial monitors of the whole-body homeodynamics. All cells require energy to perform their basic functions. One of the most important metabolic skills of the cell is the ability to optimally adapt metabolism according to demand or availability, known as metabolic flexibility. The immune cells, first line of host defense that circulate in the body and migrate between tissues, need to function also in environments in which nutrients are not always available. The resilience of immune cells consists precisely in their high adaptive capacity, a challenge that arises especially in the framework of sustained immune responses. Pubmed and Scopus databases were consulted to construct the extensive background explored in this review, from the Kennedy and Lehninger studies on mitochondrial biochemistry of the 1950s to the most recent findings on immunometabolism. In detail, we first focus on how metabolic reconfiguration influences the action steps of the immune system and modulates immune cell fate and function. Then, we highlighted the evidence for considering mitochondria, besides conventional cellular energy suppliers, as the powerhouses of immunometabolism. Finally, we explored the main immunometabolic hubs in the organism emphasizing in them the reciprocal impact between metabolic and immune components in both physiological and pathological conditions.
Topics: Immune System; Mitochondria; Energy Metabolism
PubMed: 38464536
DOI: 10.3389/fimmu.2024.1334006 -
Cancer Immunology Research Oct 2023Hematopoietic stem cells (HSC) and T cells are intimately related, lineage-dependent cell populations that are extensively used as therapeutic products for the treatment...
Hematopoietic stem cells (HSC) and T cells are intimately related, lineage-dependent cell populations that are extensively used as therapeutic products for the treatment of hematologic malignancies and certain types of solid tumors. These cellular therapies can be life-saving treatments; however, their efficacies are often limited by factors influencing their activity and cellular properties. Among these factors is mitochondrial metabolism, which influences the function and fate commitment of both HSCs and T cells. Mitochondria, besides being the "cellular powerhouse," provide metabolic intermediates that are used as substrates for epigenetic modifications and chromatin remodeling, thus, driving cell fate decisions during differentiation. Moreover, mitochondrial fitness and mitochondrial quality control mechanisms are closely related to cellular function, and impairment of these mitochondrial properties associates with cellular dysfunction due to factors such as T-cell exhaustion and aging. Here, we give an overview of the role of mitochondria in shaping the behavior of these lineage-related cell populations. Moreover, we discuss the potential of novel mitochondria-targeting strategies for enhancing HSC- and T cell-based cancer immunotherapies and highlight how design and application of such approaches requires consideration of the metabolic similarities and differences between HSCs and T cells. See related article on p. 1302.
Topics: T-Lymphocytes; Hematopoietic Stem Cells; Cell Differentiation; Mitochondria
PubMed: 37789763
DOI: 10.1158/2326-6066.CIR-22-0685 -
Mitochondrion Sep 2023Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease characterized by the damage of insulin-secreting β-cells in the pancreatic islets of Langerhans.... (Review)
Review
Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease characterized by the damage of insulin-secreting β-cells in the pancreatic islets of Langerhans. To date, its etiology is not fully understood, despite decades of active search for root causes, and that underlines the complexity of the disease pathogenesis. It was found that mitophagy plays a regulatory role in the development of autoimmune response during T1DM pathogenesis by preventing the accumulation of defective/dysfunctional mitochondria in pancreatic cells. Mitochondrial dysfunction due to impaired mitophagy with the release of mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA) contributes to initiating an inflammatory response by elevating pro-inflammatory cytokines and interacting with receptors like those involved in the pathogen-associated response. Moreover, mtROS and mtDNA activate pathways leading to the development of chronic inflammation, which is tightly implicated in T1DM autoimmunity. In this review, we summarized the evidence highlighting the functional role of mitophagy and mitochondria in the development of immune response and chronic inflammation during T1DM pathogenesis. Several anti-inflammatory and mitophagy-related treatment options have been explored.
Topics: Humans; Diabetes Mellitus, Type 1; Mitophagy; Mitochondria; DNA, Mitochondrial; Inflammation; Reactive Oxygen Species
PubMed: 37453498
DOI: 10.1016/j.mito.2023.07.002 -
Mitochondrion Sep 2023Mitochondrial transplantation is a promising solution for the heart following ischemia-reperfusion injury due to its capacity to replace damaged mitochondria and restore... (Review)
Review
Mitochondrial transplantation is a promising solution for the heart following ischemia-reperfusion injury due to its capacity to replace damaged mitochondria and restore cardiac function. However, many barriers (such as inadequate mitochondrial internalization, poor survival of transplanted mitochondria, few mitochondria colocalized with cardiac cells) compromise the replacement of injured mitochondria with transplanted mitochondria. Therefore, it is necessary to optimize mitochondrial transplantation therapy to improve clinical effectiveness. By analogy, myocardial ischemia-reperfusion injury is like a withered flower, it needs to absorb enough nutrients to recover and bloom. In this review, we present a comprehensive overview of "nutrients" (source of exogenous mitochondria and different techniques for mitochondrial isolation), "absorption" (mitochondrial transplantation approaches, mitochondrial transplantation dose and internalization mechanism), and "flowering" (the mechanism of mitochondrial transplantation in cardioprotection) for myocardial ischemia-reperfusion injury.
Topics: Humans; Myocardial Reperfusion Injury; Mitochondria, Heart; Heart
PubMed: 37549815
DOI: 10.1016/j.mito.2023.08.001 -
Discovery Medicine Oct 2023Mitochondria-associated membranes (MAMs) play a significant role in multiple cellular processes including lipid metabolism and neuronal survival. Fatty acids constitute... (Review)
Review
Mitochondria-associated membranes (MAMs) play a significant role in multiple cellular processes including lipid metabolism and neuronal survival. Fatty acids constitute 80% of the dry mass of the brain and are vital for life. Apart from mitochondrial β-oxidation, fatty acids are metabolized in part by peroxisomes to regulate the generation of acyl Coenzyme A and adenosine triphosphate (ATP). Ablation of mitochondria and its associated genes tether endoplasmic reticulum (ER)-Mitochondria contact and results in loss of function leading to aberrant lipid metabolism. Additionally, an increase in reactive oxygen species (ROS) levels along with free radicals' generation may lead to alteration in the integrity of membrane phospholipids, proteins, and DNA. Hence, it is critical to understand the effect of structural and functional aspects of mitochondria on lipid homeostasis. This review explains the role of mitochondrial dysfunction in lipid metabolism and its impact on various neurodegenerative diseases and metabolic disorders.
Topics: Humans; Mitochondria; Reactive Oxygen Species; Homeostasis; Fatty Acids; Lipids
PubMed: 37811607
DOI: 10.24976/Discov.Med.202335178.64 -
Biochemistry. Biokhimiia Nov 2023The evolution of mitochondria has proceeded independently in different eukaryotic lines, which is reflected in the diversity of mitochondrial genomes and mechanisms of... (Review)
Review
The evolution of mitochondria has proceeded independently in different eukaryotic lines, which is reflected in the diversity of mitochondrial genomes and mechanisms of their expression in eukaryotic species. Mitochondria have lost most of bacterial ancestor genes by transferring them to the nucleus or eliminating them. However, mitochondria of almost all eukaryotic cells still retain relatively small genomes, as well as their replication, transcription, and translation apparatuses. The dependence on the nuclear genome, specific features of mitochondrial transcripts, and synthesis of highly hydrophobic membrane proteins in the mitochondria have led to significant changes in the translation apparatus inherited from the bacterial ancestor, which retained the basic structure necessary for protein synthesis but became more specialized and labile. In this review, we discuss specific properties of translation initiation in the mitochondria and how the evolution of mitochondria affected the functions of main factors initiating protein biosynthesis in these organelles.
Topics: Mitochondria; Protein Biosynthesis; Genome, Mitochondrial; Mitochondrial Proteins
PubMed: 38105202
DOI: 10.1134/S0006297923110135 -
Free Radical Biology & Medicine Nov 2023Aging is a complex biological process characterized by a progressive decline in cellular and tissue function, ultimately leading to organismal aging. Stem cells, with... (Review)
Review
Aging is a complex biological process characterized by a progressive decline in cellular and tissue function, ultimately leading to organismal aging. Stem cells, with their regenerative potential, play a crucial role in maintaining tissue homeostasis and repair throughout an organism's lifespan. Mitochondria, the powerhouses of the cell, have emerged as key players in the aging process, impacting stem cell function and contributing to age-related tissue dysfunction. Here are discuss the mechanisms through which mitochondria influence stem cell fate decisions, including energy production, metabolic regulation, ROS signalling, and epigenetic modifications. Therefore, this review highlights the role of mitochondria in driving stem cell senescence and the subsequent impact on tissue function, leading to overall organismal aging and age-related diseases. Finally, we explore potential anti-aging therapies targeting mitochondrial health and discuss their implications for promoting healthy aging. This comprehensive review sheds light on the critical interplay between mitochondrial function, stem cell senescence, and organismal aging, offering insights into potential strategies for attenuating age-related decline and promoting healthy longevity.
Topics: Cellular Senescence; Mitochondria; Cell Differentiation; Stem Cells
PubMed: 37739140
DOI: 10.1016/j.freeradbiomed.2023.09.019 -
Mitochondrion Sep 2023Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed... (Review)
Review
Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed specialized purposes for a very long time. But in recentpast years, scientists have learned that organelles become dynamic and make physical contact. Additionally, Biological processes are regulated by organelles interactions and its alteration play an important role in cell malfunctioning and several pathologies, including neurodegenerative diseases. Mitochondrial-ER contact sites (MERCS) have received considerable attention in the domain of cell homeostasis and dysfunction, specifically in the area of neurodegeneration. This is largely due to the significant role of this subcellular compartment in a diverse array of vital cellular functions, including Ca homeostasis, transport, bioenergetics and turnover, mitochondrial dynamics, apoptotic signaling, ER stress, and inflammation. A significant number of disease-associated proteins were found to physically interact with the ER-Mitochondria (ER-MT) interface, causing structural and/or functional alterations in this compartment. In this review, we summarize current knowledge about the structure and functions of the ER-MT contact sites, as well as the possible repercussions of their alteration in notable neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and fronto-temporal dementia. The constraints and complexities in defining the nature and origin of the highlighted defects in ER-MT communication, as well as their concise contribution to the neurodegenerative process, are illustrated in particular. The possibility of using MERCS as a potential drug target to prevent neuronal damage and ultimately neurodegeneration is the topic of our final discussion.
Topics: Humans; Endoplasmic Reticulum; Mitochondria; Mitochondrial Membranes; Neurodegenerative Diseases; Parkinson Disease
PubMed: 37495165
DOI: 10.1016/j.mito.2023.07.005 -
Basic Research in Cardiology Sep 2023Giant mitochondria are frequently observed in different disease models within the brain, kidney, and liver. In cardiac muscle, these enlarged organelles are present... (Review)
Review
Giant mitochondria are frequently observed in different disease models within the brain, kidney, and liver. In cardiac muscle, these enlarged organelles are present across diverse physiological and pathophysiological conditions including in ageing and exercise, and clinically in alcohol-induced heart disease and various cardiomyopathies. This mitochondrial aberration is widely considered an early structural hallmark of disease leading to adverse organ function. In this thematic paper, we discuss the current state-of-knowledge on the presence, structure and functional implications of giant mitochondria in heart muscle. Despite its demonstrated reoccurrence in different heart diseases, the literature on this pathophysiological phenomenon remains relatively sparse since its initial observations in the early 60s. We review historical and contemporary investigations from cultured cardiomyocytes to human tissue samples to address the role of giant mitochondria in cardiac health and disease. Finally, we discuss their significance for the future development of novel mitochondria-targeted therapies to improve cardiac metabolism and functionality.
Topics: Humans; Myocytes, Cardiac; Mitochondrial Swelling; Mitochondria; Cardiomyopathies; Myocardium; Mitochondria, Heart
PubMed: 37775647
DOI: 10.1007/s00395-023-01011-3 -
Nature Communications Jul 2023The hard tick, Ixodes ricinus, a main Lyme disease vector, harbors an intracellular bacterial endosymbiont. Midichloria mitochondrii is maternally inherited and resides...
The hard tick, Ixodes ricinus, a main Lyme disease vector, harbors an intracellular bacterial endosymbiont. Midichloria mitochondrii is maternally inherited and resides in the mitochondria of I. ricinus oocytes, but the consequences of this endosymbiosis are not well understood. Here, we provide 3D images of wild-type and aposymbiotic I. ricinus oocytes generated with focused ion beam-scanning electron microscopy. Quantitative image analyses of endosymbionts and oocyte mitochondria at different maturation stages show that the populations of both mitochondrion-associated bacteria and bacterium-hosting mitochondria increase upon vitellogenisation, and that mitochondria can host multiple bacteria in later stages. Three-dimensional reconstructions show symbiosis-dependent morphologies of mitochondria and demonstrate complete M. mitochondrii inclusion inside a mitochondrion. Cytoplasmic endosymbiont located close to mitochondria are not oriented towards the mitochondria, suggesting that bacterial recolonization is unlikely. We further demonstrate individual globular-shaped mitochondria in the wild type oocytes, while aposymbiotic oocytes only contain a mitochondrial network. In summary, our study suggests that M. mitochondrii modulates mitochondrial fragmentation in oogenesis possibly affecting organelle function and ensuring its presence over generations.
Topics: Imaging, Three-Dimensional; Rickettsiales; Oocytes; Mitochondria; Cytoplasm
PubMed: 37438329
DOI: 10.1038/s41467-023-39758-x