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Cells May 2023The mitochondrion has a unique position among other cellular organelles due to its dynamic properties and symbiotic nature, which is reflected in an active exchange of... (Review)
Review
The mitochondrion has a unique position among other cellular organelles due to its dynamic properties and symbiotic nature, which is reflected in an active exchange of metabolites and cofactors between the rest of the intracellular compartments. The mitochondrial energy metabolism is greatly dependent on nicotinamide adenine dinucleotide (NAD) as a cofactor that is essential for both the activity of respiratory and TCA cycle enzymes. The NAD level is determined by the rate of NAD synthesis, the activity of NAD-consuming enzymes, and the exchange rate between the individual subcellular compartments. In this review, we discuss the NAD synthesis pathways, the NAD degradation enzymes, and NAD subcellular localization, as well as NAD transport mechanisms with a focus on mitochondria. Finally, the effect of the pathologic depletion of mitochondrial NAD pools on mitochondrial proteins' post-translational modifications and its role in neurodegeneration will be reviewed. Understanding the physiological constraints and mechanisms of NAD maintenance and the exchange between subcellular compartments is critical given NAD's broad effects and roles in health and disease.
Topics: NAD; Mitochondria; Homeostasis; Organelles; Energy Metabolism
PubMed: 37174729
DOI: 10.3390/cells12091329 -
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 -
Neural Plasticity 2020Sensorineural hearing loss (SNHL) becomes an inevitable worldwide public health issue, and deafness treatment is urgently imperative; yet their current curative therapy... (Review)
Review
Sensorineural hearing loss (SNHL) becomes an inevitable worldwide public health issue, and deafness treatment is urgently imperative; yet their current curative therapy is limited. Auditory neuropathies (AN) were proved to play a substantial role in SNHL recently, and spiral ganglion neuron (SGN) dysfunction is a dominant pathogenesis of AN. Auditory pathway is a high energy consumption system, and SGNs required sufficient mitochondria. Mitochondria are known treatment target of SNHL, but mitochondrion mechanism and pathology in SGNs are not valued. Mitochondrial dysfunction and pharmacological therapy were studied in neurodegeneration, providing new insights in mitochondrion-targeted treatment of AN. In this review, we summarized mitochondrial biological functions related to SGNs and discussed interaction between mitochondrial dysfunction and AN, as well as existing mitochondrion treatment for SNHL. Pharmaceutical exploration to protect mitochondrion dysfunction is a feasible and effective therapeutics for AN.
Topics: Animals; Auditory Pathways; Hearing Loss, Central; Humans; Mice; Mitochondria; Neurons; Spiral Ganglion
PubMed: 32908487
DOI: 10.1155/2020/8843485 -
Autoimmunity Dec 2022Systemic lupus erythematosus (SLE) is a heterogeneous, multisystemic autoimmune disease with a broad clinical spectrum. Loss of self-tolerance and chronic inflammation... (Review)
Review
Systemic lupus erythematosus (SLE) is a heterogeneous, multisystemic autoimmune disease with a broad clinical spectrum. Loss of self-tolerance and chronic inflammation are critical markers of SLE pathogenesis. Although alterations in adaptive immunity are widely recognized, increasing reports indicate the role of mitochondrial dysfunction in activating pathogenic pathways involving the innate immune system. Among these, disarrangements in mitochondrial DNA copy number and heteroplasmy percentage are related to SLE activity. Furthermore, increased oxidative stress contributes to post-translational changes in different molecules (proteins, nucleic acids, and lipids), release of oxidized mitochondrial DNA through a pore of voltage-dependent anion channel oligomers, and spontaneous mitochondrial antiviral signaling protein oligomerization. Finally, a reduction in mitophagy, apoptosis induction, and NETosis has been reported in SLE. Most of these pathways lead to persistent and inappropriate exposure to oxidized mitochondrial DNA, which can stimulate plasmacytoid dendritic cells, enhance autoreactive lymphocyte activation, and release increased amounts of interferons through stimulation of toll-like receptors and cytosolic DNA sensors. Likewise, abnormal T-cell receptor activation, decreased regulatory T cells, enhanced Th17 phenotypes, and increased monocyte maturation to dendritic cells have also been observed in SLE. Targeting the players involved in mitochondrial damage can ultimately help.
Topics: Antiviral Agents; DNA, Mitochondrial; Humans; Interferons; Lipids; Lupus Erythematosus, Systemic; Mitochondria; Receptors, Antigen, T-Cell; Toll-Like Receptors
PubMed: 35978536
DOI: 10.1080/08916934.2022.2112181 -
Journal of Molecular Endocrinology Jan 2021Aging is a degenerative process that results from the accumulation of cellular and tissue lesions, leading progressively to organ dysfunction and death. Although the... (Review)
Review
Aging is a degenerative process that results from the accumulation of cellular and tissue lesions, leading progressively to organ dysfunction and death. Although the biological basis of human aging remains unclear, a large amount of data points to deregulated mitochondrial function as a central regulator of this process. Mounting years of research on aging support the notion that the engendered age-related decline of mitochondria is associated with alterations in key pathways that regulate mitochondrial biology. Particularly, several studies in the last decade have emphasized the importance of the estrogen-related receptor (ERR) family of nuclear receptors, master regulators of mitochondrial function, and their transcriptional coactivators PGC-1s in this context. In this review, we summarize key discoveries implicating the PGC-1/ERR axis in age-associated mitochondrial deregulation and tissue dysfunction. Also, we highlight the pharmacological potential of targeting the PGC-1/ERR axis to alleviate the onset of aging and its adverse effects.
Topics: Aging; Animals; Biomarkers; Cellular Senescence; Humans; Mitochondria; Receptors, Estrogen; Signal Transduction; Transcription Factors
PubMed: 33112791
DOI: 10.1530/JME-20-0196 -
Free Radical Biology & Medicine Jan 2022Mitochondria participate in essential cellular functions, including energy production, metabolism, redox homeostasis regulation, intracellular Ca handling, apoptosis,... (Review)
Review
Mitochondria participate in essential cellular functions, including energy production, metabolism, redox homeostasis regulation, intracellular Ca handling, apoptosis, and cell fate determination. Disruption of mitochondrial homeostasis under pathological conditions results in mitochondrial reactive oxygen species (ROS) generation and energy insufficiency, which further disturb mitochondrial and cellular homeostasis in a deleterious loop. Mitochondrial redox status has therefore become a potential target for therapy against cardiovascular diseases. In this review, we highlight recent progress in determining the roles of mitochondrial processes in regulating mitochondrial redox status, including mitochondrial dynamics (fusion-fission pathways), mitochondrial cristae remodeling, mitophagy, biogenesis, and mitochondrion-organelle interactions (endoplasmic reticulum-mitochondrion interactions, nucleus-mitochondrion communication, and lipid droplet-mitochondrion interactions). The strategies that activate vagal system include direct vagal activation (electrical vagal stimulation and administration of vagal neurotransmitter acetylcholine) and pharmacological modulation (choline and cholinesterase inhibitors). The vagal system plays an important role in maintaining mitochondrial homeostasis and suppressing mitochondrial oxidative stress by promoting mitochondrial biogenesis and mitophagy, moderating mitochondrial fusion and fission, strengthening mitochondrial cristae stabilization, regulating mitochondrion-organelle interactions, and inhibiting mitochondrial Ca overload. Therefore, enhancement of vagal activity can maintain mitochondrial homeostasis and represents a promising therapeutic strategy for cardiovascular diseases.
Topics: Cardiovascular Diseases; Homeostasis; Humans; Mitochondria; Mitochondrial Dynamics; Oxidation-Reduction
PubMed: 34906725
DOI: 10.1016/j.freeradbiomed.2021.12.255 -
Expert Review of Endocrinology &... Mar 2024Type 2 diabetes (T2D) presents significant global health and economic challenges, contributing to complications such as stroke, cardiovascular disease, kidney... (Review)
Review
INTRODUCTION
Type 2 diabetes (T2D) presents significant global health and economic challenges, contributing to complications such as stroke, cardiovascular disease, kidney dysfunction, and cancer. The current review explores the crucial role of mitochondria, essential for fuel metabolism, in diabetes-related processes.
AREAS COVERED
Mitochondrial deficits impact insulin-resistant skeletal muscles, adipose tissue, liver, and pancreatic β-cells, affecting glucose and lipid balance. Exercise emerges as a key factor in enhancing mitochondrial function, thereby reducing insulin resistance. Additionally, the therapeutic potential of mitochondrial uncoupling, which generates heat instead of ATP, is discussed. We explore the intricate link between mitochondrial function and diabetes, investigating genetic interventions to mitigate diabetes-related complications. We also cover the impact of insulin deficiency on mitochondrial function, the role of exercise in addressing mitochondrial defects in insulin resistance, and the potential of mitochondrial uncoupling. Furthermore, a comprehensive analysis of Mitochondrial Replacement Therapies (MRT) techniques is presented.
EXPERT OPINION
MRTs hold promise in preventing the transmission of mitochondrial disease. However, addressing ethical, regulatory, and technical considerations is crucial. Integrating mitochondrial-based treatments requires a careful balance between innovation and safety. Ethical dimensions and regulatory aspects of MRT are examined, emphasizing collaborative efforts for the responsible advancement of human health.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Mitochondria; Insulin; Glucose
PubMed: 38347803
DOI: 10.1080/17446651.2024.2307526 -
Mitochondrion May 2024Space is a challenging environment that deregulates individual homeostasis. The main external hazards associated with spaceflight include ionizing space radiation,... (Review)
Review
Space is a challenging environment that deregulates individual homeostasis. The main external hazards associated with spaceflight include ionizing space radiation, microgravity, isolation and confinement, distance from Earth, and hostile environment. Characterizing the biological responses to spaceflight environment is essential to validate the health risks, and to develop effective protection strategies. Mitochondria energetics is a key mechanism underpinning many physiological, ecological and evolutionary processes. Moreover, mitochondrial stress can be considered one of the fundamental features of space travel. So, we attempt to synthesize key information regarding the extensive effects of spaceflight on mitochondria. In summary, mitochondria are affected by all of the five main hazards of spaceflight at multiple levels, including their morphology, respiratory function, protein, and genetics, in various tissues and organ systems. We emphasize that investigating mitochondrial biology in spaceflight conditions should become the central focus of research on the impacts of spaceflight on human health, as this approach will help resolve numerous challenges of space health and combat several health disorders associated with mitochondrial dysfunction.
Topics: Space Flight; Humans; Mitochondria; Weightlessness; Stress, Physiological; Animals
PubMed: 38403094
DOI: 10.1016/j.mito.2024.101855 -
Mitochondrion Sep 2020Mitochondria are eukaryotic organelles known best for their roles in energy production and metabolism. While often thought of as simply the 'powerhouse of the cell,'... (Review)
Review
Mitochondria are eukaryotic organelles known best for their roles in energy production and metabolism. While often thought of as simply the 'powerhouse of the cell,' these organelles participate in a variety of critical cellular processes including reactive oxygen species (ROS) production, regulation of programmed cell death, modulation of inter- and intracellular nutrient signaling pathways, and maintenance of cellular proteostasis. Disrupted mitochondrial function is a hallmark of eukaryotic aging, and mitochondrial dysfunction has been reported to play a role in many aging-related diseases. While mitochondria are major players in human diseases, significant questions remain regarding their precise mechanistic role. In this review, we detail mechanisms by which mitochondrial dysfunction participate in disease and aging based on findings from model organisms and human genetics studies.
Topics: Aging; Apoptosis; Energy Metabolism; Humans; Mitochondria; Oxidative Stress; Proteostasis; Reactive Oxygen Species
PubMed: 32738358
DOI: 10.1016/j.mito.2020.07.007