-
Developmental Cell Apr 2021Mitochondria are essential organelles that execute and coordinate various metabolic processes in the cell. Mitochondrial dysfunction severely affects cell fitness and... (Review)
Review
Mitochondria are essential organelles that execute and coordinate various metabolic processes in the cell. Mitochondrial dysfunction severely affects cell fitness and contributes to disease. Proper organellar function depends on the biogenesis and maintenance of mitochondria and its >1,000 proteins. As a result, the cell has evolved mechanisms to coordinate protein and organellar quality control, such as the turnover of proteins via mitochondria-associated degradation, the ubiquitin-proteasome system, and mitoproteases, as well as the elimination of mitochondria through mitophagy. Specific quality control mechanisms are engaged depending upon the nature and severity of mitochondrial dysfunction, which can also feed back to elicit transcriptional or proteomic remodeling by the cell. Here, we will discuss the current understanding of how these different quality control mechanisms are integrated and overlap to maintain protein and organellar quality and how they may be relevant for cellular and organismal health.
Topics: Mitochondria; Mitochondrial Dynamics; Mitochondrial Membranes; Mitochondrial Proteins; Mitophagy; Peptide Hydrolases; Proteasome Endopeptidase Complex; Protein Transport; Transcription, Genetic; Ubiquitin
PubMed: 33662258
DOI: 10.1016/j.devcel.2021.02.009 -
Genetics Nov 2017Mitochondria are best known for harboring pathways involved in ATP synthesis through the tricarboxylic acid cycle and oxidative phosphorylation. Major advances in... (Review)
Review
Mitochondria are best known for harboring pathways involved in ATP synthesis through the tricarboxylic acid cycle and oxidative phosphorylation. Major advances in understanding these roles were made with mutants affecting key components of the metabolic pathways. These mutants have not only helped elucidate some of the intricacies of metabolism pathways, but they have also served as jumping off points for pharmacology, toxicology, and aging studies. The field of mitochondria research has also undergone a renaissance, with the increased appreciation of the role of mitochondria in cell processes other than energy production. Here, we focus on discoveries that were made using , with a few excursions into areas that were studied more thoroughly in other organisms, like mitochondrial protein import in yeast. Advances in mitochondrial biogenesis and membrane dynamics were made through the discoveries of novel functions in mitochondrial fission and fusion proteins. Some of these functions were only apparent through the use of diverse model systems, such as Studies of stress responses, exemplified by mitophagy and the mitochondrial unfolded protein response, have also benefitted greatly from the use of model organisms. Recent developments include the discoveries in of cell autonomous and nonautonomous pathways controlling the mitochondrial unfolded protein response, as well as mechanisms for degradation of paternal mitochondria after fertilization. The evolutionary conservation of many, if not all, of these pathways ensures that results obtained with are equally applicable to studies of human mitochondria in health and disease.
Topics: Animals; Citric Acid Cycle; Electron Transport; Mitochondria; Organelle Biogenesis
PubMed: 29097398
DOI: 10.1534/genetics.117.300262 -
Journal of Enzyme Inhibition and... Dec 2021COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes... (Review)
Review
COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19.
Topics: Antiviral Agents; COVID-19; Humans; Mitochondria; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34107824
DOI: 10.1080/14756366.2021.1937144 -
The FEBS Journal Nov 2022With the development of advanced technologies, many small open reading frames (sORFs) have been found to be translated into micropeptides. Interestingly, a considerable... (Review)
Review
With the development of advanced technologies, many small open reading frames (sORFs) have been found to be translated into micropeptides. Interestingly, a considerable proportion of micropeptides are located in mitochondria, which are designated here as mitochondrion-located peptides (MLPs). These MLPs often contain a transmembrane domain and show a high degree of conservation across species. They usually act as co-factors of large proteins and play regulatory roles in mitochondria such as electron transport in the respiratory chain, reactive oxygen species (ROS) production, metabolic homeostasis, and so on. Deficiency of MLPs disturbs diverse physiological processes including immunity, differentiation, and metabolism both in vivo and in vitro. These findings reveal crucial functions for MLPs and provide fresh insights into diverse mitochondrion-associated biological processes and diseases.
Topics: Open Reading Frames; Peptides; Mitochondria
PubMed: 35599630
DOI: 10.1111/febs.16532 -
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 -
Trends in Microbiology Feb 2019Arguments based on cell energetics favour the view that a mitochondrion capable of oxidative phosphorylation was a prerequisite for the evolution of other features of... (Review)
Review
Arguments based on cell energetics favour the view that a mitochondrion capable of oxidative phosphorylation was a prerequisite for the evolution of other features of the eukaryotic cell, including increased volume, genome size and, eventually, phagotrophy. Contrary to this we argue that: (i) extant amitochondriate eukaryotes possess voluminous phagotrophic cells with large genomes; (ii) picoeukaryotes demonstrate that phagotrophy is feasible at prokaryotic cell sizes; and (iii) the assumption that evolution of complex features requires extra ATP, often mentioned in this context, is unfounded and should not be used in such considerations. We claim that the diversity of cell organisations and functions observed today in eukaryotes gives no reason to postulate that a mitochondrion must have preceded phagocytosis in eukaryogenesis.
Topics: Adenosine Triphosphate; Archaea; Biological Evolution; Eukaryota; Eukaryotic Cells; Genome; Mitochondria; Phagocytosis; Prokaryotic Cells; Symbiosis
PubMed: 30466901
DOI: 10.1016/j.tim.2018.10.005 -
Mitochondrion Mar 2018Human mitochondria are descendants of microbes and altered mitochondrial function has been implicated in processes ranging from ageing to diabetes. Recent work has... (Review)
Review
Human mitochondria are descendants of microbes and altered mitochondrial function has been implicated in processes ranging from ageing to diabetes. Recent work has highlighted the importance of gut microbial communities in human health and disease. While the spotlight has been on the influence of such communities on the human immune system and the extraction of calories from otherwise indigestible food, an important but less investigated link between the microbes and mitochondria remains unexplored. Microbial metabolites including short chain fatty acids as well as other molecules such as pyrroloquinoline quinone, fermentation gases, and modified fatty acids influence mitochondrial function. This review focuses on the known direct and indirect effects of microbes upon mitochondria and speculates regarding additional links for which there is circumstantial evidence. Overall, while there is compelling evidence that a microbiota-mitochondria link exists, explicit and holistic mechanistic studies are warranted to advance this nascent field.
Topics: Fatty Acids, Volatile; Fermentation; Health; Humans; Metabolism; Microbiota; Mitochondria; Pyrroles; Quinolines
PubMed: 28838618
DOI: 10.1016/j.mito.2017.08.008 -
Annual Review of Microbiology 2010The discovery of mitochondrion-type genes in organisms thought to lack mitochondria led to the demonstration that hydrogenosomes share a common ancestry with... (Review)
Review
The discovery of mitochondrion-type genes in organisms thought to lack mitochondria led to the demonstration that hydrogenosomes share a common ancestry with mitochondria, as well as the discovery of mitosomes in multiple eukaryotic lineages. No examples of examined eukaryotes lacking a mitochondrion-related organelle exist, implying that the endosymbiont that gave rise to the mitochondrion was present in the first eukaryote. These organelles, known as hydrogenosomes, mitosomes, or mitochondrion-like organelles, are typically reduced, both structurally and biochemically, relative to classical mitochondria. However, despite their diversification and adaptation to different niches, all appear to play a role in Fe-S cluster assembly, as observed for mitochondria. Although evidence supports the use of common protein targeting mechanisms in the biogenesis of these diverse organelles, divergent features are also apparent. This review examines the metabolism and biogenesis of these organelles in divergent unicellular microbes, with a focus on parasitic protists.
Topics: Eukaryota; Genes, Mitochondrial; Iron-Sulfur Proteins; Metabolic Networks and Pathways; Mitochondria; Phylogeny; Sequence Homology
PubMed: 20528687
DOI: 10.1146/annurev.micro.62.081307.162826 -
Oxidative Medicine and Cellular... 2016Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular... (Review)
Review
Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders.
Topics: Acute Disease; Administration, Oral; Animals; Antioxidants; Humans; Mitochondria; Reactive Oxygen Species; Respiratory Burst
PubMed: 26649144
DOI: 10.1155/2016/6859523 -
Trends in Parasitology Mar 2017Rapid emergence of resistance to atovaquone, which targets electron transport in the malaria parasite mitochondrion, relegated its use to prophylaxis and even cast a... (Review)
Review
Rapid emergence of resistance to atovaquone, which targets electron transport in the malaria parasite mitochondrion, relegated its use to prophylaxis and even cast a shadow over the development of drugs targeting other parasite mitochondrial pathways. Here we argue for a renewed focus on the mitochondrion as a drug target, focusing particularly on the issues of resistance. We posit a hypothesis for why atovaquone resistance emerges so quickly, and we explain how facile acquisition of resistance is apparently offset by an inability of parasites to spread this resistance. We also explore the utility and resistance issues for emerging new drugs targeting parasite mitochondria, concluding that the mitochondrion is indeed an excellent target.
Topics: Antimalarials; Atovaquone; Drug Delivery Systems; Drug Resistance; Humans; Malaria; Mitochondria; Plasmodium falciparum
PubMed: 27789127
DOI: 10.1016/j.pt.2016.10.002