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Cellular and Molecular Life Sciences :... Sep 2020Endosymbiosis and organellogenesis are virtually unknown among prokaryotes. The single presumed example is the endosymbiogenetic origin of mitochondria, which is hidden... (Review)
Review
Endosymbiosis and organellogenesis are virtually unknown among prokaryotes. The single presumed example is the endosymbiogenetic origin of mitochondria, which is hidden behind the event horizon of the last eukaryotic common ancestor. While eukaryotes are monophyletic, it is unlikely that during billions of years, there were no other prokaryote-prokaryote endosymbioses as symbiosis is extremely common among prokaryotes, e.g., in biofilms. Therefore, it is even more precarious to draw conclusions about potentially existing (or once existing) prokaryotic endosymbioses based on a single example. It is yet unknown if the bacterial endosymbiont was captured by a prokaryote or by a (proto-)eukaryote, and if the process of internalization was parasitic infection, slow engulfment, or phagocytosis. In this review, we accordingly explore multiple mechanisms and processes that could drive the evolution of unicellular microbial symbioses with a special attention to prokaryote-prokaryote interactions and to the mitochondrion, possibly the single prokaryotic endosymbiosis that turned out to be a major evolutionary transition. We investigate the ecology and evolutionary stability of inter-species microbial interactions based on dependence, physical proximity, cost-benefit budget, and the types of benefits, investments, and controls. We identify challenges that had to be conquered for the mitochondrial host to establish a stable eukaryotic lineage. Any assumption about the initial interaction of the mitochondrial ancestor and its contemporary host based solely on their modern relationship is rather perilous. As a result, we warn against assuming an initial mutually beneficial interaction based on modern mitochondria-host cooperation. This assumption is twice fallacious: (i) endosymbioses are known to evolve from exploitative interactions and (ii) cooperativity does not necessarily lead to stable mutualism. We point out that the lack of evidence so far on the evolution of endosymbiosis from mutual syntrophy supports the idea that mitochondria emerged from an exploitative (parasitic or phagotrophic) interaction rather than from syntrophy.
Topics: Biological Evolution; Eukaryotic Cells; Microbial Consortia; Mitochondria; Mitochondrial ADP, ATP Translocases; Plastids; Prokaryotic Cells; Symbiosis
PubMed: 32008087
DOI: 10.1007/s00018-020-03462-6 -
Oxidative Medicine and Cellular... 2019
Topics: Animals; Antioxidants; Cell Death; Cell Survival; Energy Metabolism; Humans; Mitochondria; Signal Transduction
PubMed: 31915504
DOI: 10.1155/2019/2608187 -
Experimental Neurology Aug 2020The mitochondrion is a double membrane structured organelle involved in a variety of regulatory functions such as calcium signaling, production of adenosine... (Review)
Review
The mitochondrion is a double membrane structured organelle involved in a variety of regulatory functions such as calcium signaling, production of adenosine triphosphate, apoptosis, reactive oxygen species generation, cell growth, and cell cycling. Impaired mitochondrial function is evident in various neurological disorders stemming from both acute and chronic neural injury. Herein, we review the role of mitochondrial regulation in maintaining cellular homeostasis, the consequences of their dysfunction in relation to pathophysiology after neurotrauma, approaches being used to promote their bioenergetic integrity for neuroprotection, and multifaceted methods being used to preserve/rescue their function following both traumatic brain and spinal cord injury.
Topics: Animals; Energy Metabolism; Humans; Mitochondria; Spinal Cord Injuries
PubMed: 32353464
DOI: 10.1016/j.expneurol.2020.113332 -
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 -
Biochimica Et Biophysica Acta.... May 2022Mitochondrion is a double membrane organelle that is responsible for cellular respiration and production of most of the ATP in eukaryotic cells. Mitochondrial DNA... (Review)
Review
Mitochondrion is a double membrane organelle that is responsible for cellular respiration and production of most of the ATP in eukaryotic cells. Mitochondrial DNA (mtDNA) is the genetic material carried by mitochondria, which encodes some essential subunits of respiratory complexes independent of nuclear DNA. Normally, mtDNA binds to certain proteins to form a nucleoid that is stable in mitochondria. Nevertheless, a variety of physiological or pathological stresses can cause mtDNA damage, and the accumulation of damaged mtDNA in mitochondria leads to mitochondrial dysfunction, which triggers the occurrence of mitochondrial diseases in vivo. In response to mtDNA damage, cell initiates multiple pathways including mtDNA repair, degradation, clearance and release, to recover mtDNA, and maintain mitochondrial quality and cell homeostasis. In this review, we provide our current understanding of the fate of damaged mtDNA, focus on the pathways and mechanisms of removing damaged mtDNA in the cell.
Topics: DNA Damage; DNA Repair; DNA, Mitochondrial; Extracellular Vesicles; Humans; Mitochondria; Mitochondrial Diseases; Mitophagy; Signal Transduction; Ubiquitin-Protein Ligases
PubMed: 35131372
DOI: 10.1016/j.bbamcr.2022.119233 -
International Journal of Molecular... Dec 2023Ubiquitination is a post-translational modification that targets specific proteins on their lysine residues. Depending on the type of ubiquitination, this modification... (Review)
Review
Ubiquitination is a post-translational modification that targets specific proteins on their lysine residues. Depending on the type of ubiquitination, this modification ultimately regulates the stability or degradation of the targeted proteins. Ubiquitination is mediated by three different classes of enzymes: the E1 ubiquitin-activating enzymes, the E2 ubiquitin-conjugating enzymes and, most importantly, the E3 ubiquitin ligases. E3 ligases are responsible for the final step of the ubiquitin cascade, interacting directly with the target proteins. E3 ligases can also be involved in DNA repair, cell cycle regulation and response to stress; alteration in their levels can be involved in oncogenic transformation and cancer progression. Of all the six hundred E3 ligases of the human genome, only three of them are specific to the mitochondrion: MARCH5, RNF185 and MUL1. Their alterations (that reflect on the alteration of the mitochondria functions) can be related to cancer progression, as underlined by the increasing research performed in recent years on these three mitochondrial enzymes. This review will focus on the function and mechanisms of the mitochondrial E3 ubiquitin ligases, as well as their important targets, in cancer development and progression, also highlighting their potential use for cancer therapy.
Topics: Humans; Ubiquitin-Protein Ligases; Ubiquitination; Ubiquitin; Proteins; Neoplasms; Mitochondria; Ubiquitin-Conjugating Enzymes; Mitochondrial Proteins
PubMed: 38139010
DOI: 10.3390/ijms242417176 -
Biomolecules Dec 2023Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis... (Review)
Review
Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich's Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR's role as a promising therapeutic target in combating these devastating disorders.
Topics: Animals; Neurodegenerative Diseases; Mitochondria; Mitochondrial Diseases; Aging; Unfolded Protein Response
PubMed: 38136659
DOI: 10.3390/biom13121789 -
International Journal of Molecular... Sep 2021In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge... (Review)
Review
In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge is still incomplete. A key issue is the difference in metabolism between normal and cancer cells. The features that distinguish cancer cells from normal cells are the increased proliferation and abnormal differentiation and maturation of these cells, which are due to regulatory changes in the emerging tumour. Normal cells use oxidative phosphorylation (OXPHOS) in the mitochondrion as a major source of energy during division. During OXPHOS, there are 36 ATP molecules produced from one molecule of glucose, in contrast to glycolysis which provides an ATP supply of only two molecules. Although aerobic glucose metabolism is more efficient, metabolism based on intensive glycolysis provides intermediate metabolites necessary for the synthesis of nucleic acids, proteins and lipids, which are in constant high demand due to the intense cell division in cancer. This is the main reason why the cancer cell does not "give up" on glycolysis despite the high demand for energy in the form of ATP. One of the evolving trends in the development of anti-cancer therapies is to exploit differences in the metabolism of normal cells and cancer cells. Currently constructed therapies, based on cell metabolism, focus on the attempt to reprogram the metabolic pathways of the cell in such a manner that it becomes possible to stop unrestrained proliferation.
Topics: Adenosine Triphosphate; Animals; Glucose; Glycolysis; Humans; Mitochondria; Neoplasms; Oxidative Phosphorylation
PubMed: 34502416
DOI: 10.3390/ijms22179507 -
Adipocyte Dec 2019Individual cell types vary enormously in the amount of different organelles they contain. One such organelle is the mitochondrion. Understanding how mitochondrial levels... (Review)
Review
Individual cell types vary enormously in the amount of different organelles they contain. One such organelle is the mitochondrion. Understanding how mitochondrial levels are controlled is essential since so many disease states seem to involve mitochondrial function. The beige adipocyte is an inducible form of adipocyte that emerges in response to cold exposure and some other external stimuli. To perform its thermogenic function, its level of mitochondria increases dramatically. If the stimuli are removed the mitochondrial levels return to base line. Following the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype through mitophagy-mediated mitochondrial degradation. The beige cell is therefore a dynamic model for studying the mechanism of mitochondrial biogenesis and degradation.
Topics: Adipocytes; Adipocytes, Beige; Adipose Tissue, Beige; Adipose Tissue, White; Animals; Humans; Mitochondria; Mitophagy; Organelle Biogenesis; Phenotype; Signal Transduction; Thermogenesis; Uncoupling Protein 1
PubMed: 30686106
DOI: 10.1080/21623945.2019.1574194