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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 -
Experimental & Molecular Medicine Dec 2023Mitochondria participate in a wide range of cellular processes. One essential function of mitochondria is to be a platform for antiviral signaling proteins during the... (Review)
Review
Mitochondria participate in a wide range of cellular processes. One essential function of mitochondria is to be a platform for antiviral signaling proteins during the innate immune response to viral infection. Recently, studies have revealed that mitochondrion-derived DNAs and RNAs are recognized as non-self molecules and act as immunogenic ligands. More importantly, the cytosolic release of these mitochondrial nucleic acids (mt-NAs) is closely associated with the pathogenesis of human diseases accompanying aberrant immune activation. The release of mitochondrial DNAs (mtDNAs) via BAX/BAK activation and/or VDAC1 oligomerization activates the innate immune response and inflammasome assembly. In addition, mitochondrial double-stranded RNAs (mt-dsRNAs) are sensed by pattern recognition receptors in the cytosol to induce type I interferon expression and initiate apoptotic programs. Notably, these cytosolic mt-NAs also mediate adipocyte differentiation and contribute to mitogenesis and mitochondrial thermogenesis. In this review, we summarize recent studies of innate immune signaling pathways regulated by mt-NAs, human diseases associated with mt-NAs, and the emerging physiological roles of mt-NAs.
Topics: Humans; Nucleic Acids; Immunity, Innate; Signal Transduction; Receptors, Pattern Recognition; Mitochondria
PubMed: 38036728
DOI: 10.1038/s12276-023-01121-x -
The International Journal of... Jun 2018Bipolar disorder is a chronic and often debilitating illness. Current treatment options (both pharmaco- and psychotherapy) have shown efficacy, but for many leave a... (Review)
Review
BACKGROUND
Bipolar disorder is a chronic and often debilitating illness. Current treatment options (both pharmaco- and psychotherapy) have shown efficacy, but for many leave a shortfall in recovery. Advances in the understanding of the pathophysiology of bipolar disorder suggest that interventions that target mitochondrial dysfunction may provide a therapeutic benefit.
METHODS
This review explores the current and growing theoretical rationale as well as existing preclinical and clinical data for those therapies aiming to target the mitochondrion in bipolar disorder. A Clinicaltrials.gov and ANZCTR search was conducted for complete and ongoing trials on mitochondrial agents used in psychiatric disorders. A PubMed search was also conducted for literature published between January 1981 and July 2017. Systematic reviews, randomized controlled trials, observational studies, case series, and animal studies with an emphasis on agents affecting mitochondrial function and its role in bipolar disorder were included. The search was augmented by manually searching the references of key papers and related literature. The results were presented as a narrative review.
RESULTS
Mitochondrial agents offer new horizons in mood disorder treatment. While some negative effects have been reported, most compounds are overall well tolerated and have generally benign side-effect profiles.
CONCLUSIONS
The study of neuroinflammation, neurodegeneration, and mitochondrial function has contributed the understanding of bipolar disorder's pathophysiology. Agents targeting these pathways could be a potential therapeutic strategy. Future directions include identification of novel candidate mitochondrial modulators as well as rigorous and well-powered clinical trials.
Topics: Animals; Antimanic Agents; Bipolar Disorder; Humans; Mitochondria
PubMed: 29596661
DOI: 10.1093/ijnp/pyy018 -
Mitochondrion Jul 2023Pulmonary fibrosis (PF) is a serious lung disease characterized by diffuse alveolitis and disruption of alveolar structure, with a poor prognosis and unclear... (Review)
Review
Pulmonary fibrosis (PF) is a serious lung disease characterized by diffuse alveolitis and disruption of alveolar structure, with a poor prognosis and unclear etiopathogenesis. While ageing, oxidative stress, metabolic disorders, and mitochondrial dysfunction have been proposed as potential contributors to the development of PF, effective treatments for this condition remain elusive. However, Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), a peptide encoded by the mitochondrial genome, has shown promising effects on glucose and lipid metabolism, cellular and mitochondrial homeostasis, as well as the reduction of systemic inflammatory responses, and is being investigated as a potential exercise mimetic. Additionally, dynamic expression changes of MOTS-c have been closely linked to ageing and ageing-related diseases, indicating its potential as an exercise mimetic. Therefore, the review aims to comprehensively analyze the available literature on the potential role of MOTS-c in improving PF development and to identify specific therapeutic targets for future treatment strategies.
Topics: Humans; Mitochondria; Peptides; Aging; Transcription Factors; Fibrosis; Mitochondrial Proteins
PubMed: 37307934
DOI: 10.1016/j.mito.2023.06.002 -
Seminars in Cancer Biology Dec 2017Mitochondria serves a primary role in energy maintenance but also function to govern levels of mitochondria-derived reactive oxygen species (mROS). ROS have long been... (Review)
Review
Mitochondria serves a primary role in energy maintenance but also function to govern levels of mitochondria-derived reactive oxygen species (mROS). ROS have long been established to play a critical role in tumorigenesis and are now considered to be integral to the regulation of diverse signaling networks that drive proliferation, tumor cell survival and malignant progression. mROS can damage DNA, activate oncogenes, block the function of tumor suppressors and drive migratory signaling. The mitochondrion's oxidant scavenging systems including SOD2, Grx2, GPrx, Trx and TrxR are key of the cellular redox tone. These mitochondrial antioxidant systems serve to tightly control the levels of the primary ROS signaling species, HO. The coordinated control of mROS levels is also coupled to the activity of the primary HO consuming enzymes of the mitochondria which are reliant on the epitranscriptomic control of selenocysteine incorporation. This review highlights the interplay between these many oncogenic signaling networks, mROS and the HO emitting and consuming capacity of the mitochondria.
Topics: Animals; Antioxidants; Cell Transformation, Neoplastic; Disease Progression; Energy Metabolism; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Mitochondria; Molecular Targeted Therapy; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 28445781
DOI: 10.1016/j.semcancer.2017.04.005 -
Mitochondrion Sep 2020
Topics: Animals; Biological Transport; Energy Metabolism; Humans; Mitochondria; Plants
PubMed: 32569844
DOI: 10.1016/j.mito.2020.06.009 -
Mitochondrion Jul 2021Mitochondria are dynamic organelles, which serve various purposes, including but not limited to the production of ATP and various metabolites, buffering ions, acting as... (Review)
Review
Mitochondria are dynamic organelles, which serve various purposes, including but not limited to the production of ATP and various metabolites, buffering ions, acting as a signaling hub, etc. In recent years, mitochondria are being seen as the central regulators of cellular growth, development, and death. Since neurons are highly specialized cells with a heavy metabolic demand, it is not surprising that neurons are one of the most mitochondria-rich cells in an animal. At synapses, mitochondrial function and dynamics is tightly regulated by synaptic calcium. Calcium influx during synaptic activity causes increased mitochondrial calcium influx leading to an increased ATP production as well as buffering of synaptic calcium. While increased ATP production is required during synaptic transmission, calcium buffering by mitochondria is crucial to prevent faulty neurotransmission and excitotoxicity. Interestingly, mitochondrial calcium also regulates the mobility of mitochondria within synapses causing mitochondria to halt at the synapse during synaptic transmission. In this review, we summarize the various roles of mitochondrial calcium at the synapse.
Topics: Animals; Calcium; Humans; Mitochondria; Mitochondrial Dynamics; Synapses; Synaptic Transmission
PubMed: 33895346
DOI: 10.1016/j.mito.2021.04.006 -
Mitochondrion May 2024Mitochondria are an indispensable part of the cell that plays a crucial role in regulating various signaling pathways, energy metabolism, cell differentiation,... (Review)
Review
Mitochondria are an indispensable part of the cell that plays a crucial role in regulating various signaling pathways, energy metabolism, cell differentiation, proliferation, and cell death. Since mitochondria have their own genetic material, they differ from their nuclear counterparts, and dysregulation is responsible for a broad spectrum of diseases. Mitochondrial dysfunction is associated with several disorders, including neuro-muscular disorders, cancer, and premature aging, among others. The intricacy of the field is due to the cross-talk between nuclear and mitochondrial genes, which has also improved our knowledge of mitochondrial functions and their pathogenesis. Therefore, interdisciplinary research and communication are crucial for mitochondrial biology and medicine due to the challenges they pose for diagnosis and treatment. The ninth annual conference of the Society for Mitochondria Research and Medicine (SMRM)- India, titled "Mitochondria in Biology and Medicine" was organized at the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India, on June 21-23, 2023. The latest advancements in the field of mitochondrial biology and medicine were discussed at the conference. In this article, we summarize the entire event for the benefit of researchers working in the field of mitochondrial biology and medicine.
Topics: Humans; Mitochondria; Mitochondrial Diseases; Animals; India
PubMed: 38423268
DOI: 10.1016/j.mito.2024.101853 -
Journal of Drug Targeting Dec 2021The liver is a vital metabolic and detoxifying organ and suffers diverse endogenous or exogenous damage. Hepatocyte mitochondria experience various structural and... (Review)
Review
The liver is a vital metabolic and detoxifying organ and suffers diverse endogenous or exogenous damage. Hepatocyte mitochondria experience various structural and functional defects from liver injury, bearing oxidative stress, metabolic dysregulation, and the disturbance of mitochondrial quality control (MQC) mechanisms. Mitochondrial malfunction initiates the mitochondria-mediated apoptotic pathways and the release of damage signals, aggravating liver damage and disease progression via inflammation and reparative fibrogenesis. Removal of mitochondrial impairment or the improvement of MQC mechanisms restore mitochondrial homeostasis and benefit liver health. This review discusses the association of mitochondrial disorders with hepatic pathophysiological processes and the resultant potential of mitochondrion-targeting therapeutics for hepatic disorders. The recent advances in the MQC mechanisms and the mitochondrial-derived damage-associated molecular patterns (DAMPs) in the pathology and treatment of liver disease are particularly focussed.
Topics: Animals; Disease Progression; Homeostasis; Humans; Inflammation; Liver Diseases; Mitochondria; Mitochondrial Diseases; Oxidative Stress
PubMed: 33788656
DOI: 10.1080/1061186X.2021.1909051 -
Molecular Human Reproduction Jan 2015
Topics: Genome, Mitochondrial; Humans; Mitochondria
PubMed: 25425605
DOI: 10.1093/molehr/gau085