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Nutrients Jan 2022Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance... (Review)
Review
Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion's survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.
Topics: Creatine; Dietary Supplements; Energy Metabolism; Exercise; Humans; Mitochondria
PubMed: 35276888
DOI: 10.3390/nu14030529 -
Mitochondrion Mar 2024Mitochondrial dynamics and autophagy play essential roles in normal cellular physiological activities, while abnormal mitochondrial dynamics and mitochondrial autophagy... (Review)
Review
Mitochondrial dynamics and autophagy play essential roles in normal cellular physiological activities, while abnormal mitochondrial dynamics and mitochondrial autophagy can cause cancer and related disorders. Abnormal mitochondrial dynamics usually occur in parallel with mitochondrial autophagy. Both have been reported to have a synergistic effect and can therefore complement or inhibit each other. Progress has been made in understanding the classical mitochondrial PINK1/Parkin pathway and mitochondrial dynamical abnormalities. Still, the mechanisms and regulatory pathways underlying the interaction between mitophagy and mitochondrial dynamics remain unexplored. Like other existing reviews, we review the molecular structure of proteins involved in mitochondrial dynamics and mitochondrial autophagy, and how their abnormalities can lead to the development of related diseases. We will also review the individual or synergistic effects of abnormal mitochondrial dynamics and mitophagy leading to cellular proliferation, differentiation and invasion. In addition, we explore the mechanisms underlying mitochondrial dynamics and mitochondrial autophagy to contribute to targeted and precise regulation of mitochondrial function. Through the study of abnormal mitochondrial dynamics and mitochondrial autophagy regulation mechanisms, as well as the role of early disease development, effective targets for mitochondrial function regulation can be proposed to enable accurate diagnosis and treatment of the associated disorders.
Topics: Mitochondrial Dynamics; Molecular Structure; Autophagy; Mitophagy; Ubiquitin-Protein Ligases; Mitochondria
PubMed: 38246334
DOI: 10.1016/j.mito.2024.101847 -
Oxidative Medicine and Cellular... 2018Mitochondria are highly dynamic and regulated organelles that historically have been defined based on their crucial role in cell metabolism. However, they are implicated... (Review)
Review
Mitochondria are highly dynamic and regulated organelles that historically have been defined based on their crucial role in cell metabolism. However, they are implicated in a variety of other important functions, making mitochondrial dysfunction an important axis in several pathological contexts. Despite that conventional biochemical and molecular biology approaches have provided significant insight into mitochondrial functionality, innovative techniques that provide a global view of the mitochondrion are still necessary. Proteomics fulfils this need by enabling accurate, systems-wide quantitative analysis of protein abundance. More importantly, redox proteomics approaches offer unique opportunities to tackle oxidative stress, a phenomenon that is intimately linked to aging, cardiovascular disease, and cancer. In addition, cutting-edge proteomics approaches reveal how proteins exert their functions in complex interaction networks where even subtle alterations stemming from early pathological states can be monitored. Here, we describe the proteomics approaches that will help to deepen the role of mitochondria in health and disease by assessing not only changes to mitochondrial protein composition but also alterations to their redox state and how protein interaction networks regulate mitochondrial function and dynamics. This review is aimed at showing the reader how the application of proteomics approaches during the last 20 years has revealed crucial mitochondrial roles in the context of aging, neurodegenerative disorders, metabolic disease, and cancer.
Topics: Humans; Mitochondria; Oxidation-Reduction; Oxidative Stress; Proteomics
PubMed: 30533169
DOI: 10.1155/2018/1435934 -
Mitochondrion Aug 2010Maternal diabetes has been demonstrated to adversely affect preimplantation embryo development and pregnancy outcomes. Emerging evidence has implicated that these... (Review)
Review
Maternal diabetes has been demonstrated to adversely affect preimplantation embryo development and pregnancy outcomes. Emerging evidence has implicated that these effects are associated with compromised oocyte competence. Several developmental defects during oocyte maturation in diabetic mice have been reported over past decades. Most recently, we further identified the structural, spatial and metabolic dysfunction of mitochondria in oocytes from diabetic mice, suggesting the impaired oocyte quality. These defects in the oocyte may be maternally transmitted to the embryo and then manifested later as developmental abnormalities in preimplantation embryo, congenital malformations, and even metabolic disease in the offspring. In this paper, we briefly review the effects of maternal diabetes on oocyte quality, with a particular emphasis on the mitochondrial dysfunction. The possible connection between dysfunctional oocyte mitochondria and reproductive failure of diabetic females, and the mechanism(s) by which maternal diabetes exerts its effects on the oocyte are also discussed.
Topics: Animals; Congenital Abnormalities; Diabetes Complications; Female; Humans; Mice; Mitochondria; Oocytes; Pregnancy
PubMed: 20226883
DOI: 10.1016/j.mito.2010.03.002 -
Biochimica Et Biophysica Acta Dec 2011The relationship between brain aging and Alzheimer's disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view... (Review)
Review
The relationship between brain aging and Alzheimer's disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself.
Topics: Aging; Alzheimer Disease; Amyloid beta-Peptides; Brain; Humans; Mitochondria
PubMed: 21920438
DOI: 10.1016/j.bbadis.2011.08.012 -
Mitochondrion Jan 2010The epigenome has been hypothesized to provide the interface between the environment and the nuclear DNA (nDNA) genes. Key factors in the environment are the... (Review)
Review
The epigenome has been hypothesized to provide the interface between the environment and the nuclear DNA (nDNA) genes. Key factors in the environment are the availability of calories and demands on the organism's energetic capacity. Energy is funneled through glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), the cellular bioenergetic systems. Since there are thousands of bioenergetic genes dispersed across the chromosomes and mitochondrial DNA (mtDNA), both cis and trans regulation of the nDNA genes is required. The bioenergetic systems convert environmental calories into ATP, acetyl-Coenzyme A (acetyl-CoA), s-adenosyl-methionine (SAM), and reduced NAD(+). When calories are abundant, ATP and acetyl-CoA phosphorylate and acetylate chromatin, opening the nDNA for transcription and replication. When calories are limiting, chromatin phosphorylation and acetylation are lost and gene expression is suppressed. DNA methylation via SAM can also be modulated by mitochondrial function. Phosphorylation and acetylation are also pivotal to regulating cellular signal transduction pathways. Therefore, bioenergetics provides the interface between the environment and the epigenome. Consistent with this conclusion, the clinical phenotypes of bioenergetic diseases are strikingly similar to those observed in epigenetic diseases (Angelman, Rett, Fragile X Syndromes, the laminopathies, cancer, etc.), and an increasing number of epigenetic diseases are being associated with mitochondrial dysfunction. This bioenergetic-epigenomic hypothesis has broad implications for the etiology, pathophysiology, and treatment of a wide range of common diseases.
Topics: Animals; DNA, Mitochondrial; Disease Models, Animal; Energy Metabolism; Epigenesis, Genetic; Humans; Mice; Mitochondria; Mitochondrial Diseases
PubMed: 19796712
DOI: 10.1016/j.mito.2009.09.006 -
Journal of Neuroinflammation Jan 2024Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by the infiltration of inflammatory cells and demyelination of nerves. Mitochondrial dysfunction... (Review)
Review
Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by the infiltration of inflammatory cells and demyelination of nerves. Mitochondrial dysfunction has been implicated in the pathogenesis of MS, as studies have shown abnormalities in mitochondrial activities, metabolism, mitochondrial DNA (mtDNA) levels, and mitochondrial morphology in immune cells of individuals with MS. The presence of mitochondrial dysfunctions in immune cells contributes to immunological dysregulation and neurodegeneration in MS. This review provided a comprehensive overview of mitochondrial dysfunction in immune cells associated with MS, focusing on the potential consequences of mitochondrial metabolic reprogramming on immune function. Current challenges and future directions in the field of immune-metabolic MS and its potential as a therapeutic target were also discussed.
Topics: Humans; Multiple Sclerosis; Mitochondria; DNA, Mitochondrial; Mitochondrial Diseases
PubMed: 38243312
DOI: 10.1186/s12974-024-03016-8 -
Current Eye Research Dec 2011The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between... (Review)
Review
The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.
Topics: DNA, Mitochondrial; Humans; Mitochondria; Mitochondrial Diseases; Oxidative Stress; Retinal Diseases
PubMed: 21978133
DOI: 10.3109/02713683.2011.607536 -
Open Biology Jan 2023The endobiotic flagellate is the only known eukaryote to have lost mitochondria and all its associated proteins in its evolutionary past. This final stage of the...
The endobiotic flagellate is the only known eukaryote to have lost mitochondria and all its associated proteins in its evolutionary past. This final stage of the mitochondrial evolutionary pathway may serve as a model to explain events at their very beginning such as the initiation of protein import. We have assessed the capability of proteins from this eukaryote to enter emerging mitochondria using a specifically designed assay. Hydrogenosomes (reduced mitochondria) of were incubated with a soluble protein pool derived from a cytosolic fraction of , and proteins entering hydrogenosomes were subsequently detected by mass spectrometry. The assay detected 19 specifically and reproducibly imported proteins, and in 14 cases the import was confirmed by the overexpression of their tagged version in . In most cases, only a small portion of the signal reached the hydrogenosomes, suggesting specific but inefficient transport. Most of these proteins represent enzymes of carbon metabolism, and none exhibited clear signatures of proteins targeted to hydrogenosomes or mitochondria, which is consistent with their inefficient import. The observed phenomenon may resemble a primaeval type of protein import which might play a role in the establishment of the organelle and shaping of its proteome in the initial stages of endosymbiosis.
Topics: Eukaryota; Protozoan Proteins; Organelles; Mitochondria; Protein Transport
PubMed: 36629021
DOI: 10.1098/rsob.220238 -
Developmental Neurobiology Mar 2018Mitochondria are dynamic organelles that undergo transport, fission, and fusion. The three main functions of mitochondria are to generate ATP, buffer cytosolic calcium,... (Review)
Review
Mitochondria are dynamic organelles that undergo transport, fission, and fusion. The three main functions of mitochondria are to generate ATP, buffer cytosolic calcium, and generate reactive oxygen species. A large body of evidence indicates that mitochondria are either primary targets for neurological disease states and nervous system injury, or are major contributors to the ensuing pathologies. However, the roles of mitochondria in the development and regeneration of axons have just begun to be elucidated. Advances in the understanding of the functional roles of mitochondria in neurons had been largely impeded by insufficient knowledge regarding the molecular mechanisms that regulate mitochondrial transport, stalling, fission/fusion, and a paucity of approaches to image and analyze mitochondria in living axons at the level of the single mitochondrion. However, technical advances in the imaging and analysis of mitochondria in living neurons and significant insights into the mechanisms that regulate mitochondrial dynamics have allowed the field to advance. Mitochondria have now been attributed important roles in the mechanism of axon extension, regeneration, and axon branching. The availability of new experimental tools is expected to rapidly increase our understanding of the functions of axonal mitochondria during both development and later regenerative attempts. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 221-237, 2018.
Topics: Animals; Axons; Cell Enlargement; Mitochondria; Nerve Regeneration
PubMed: 29030922
DOI: 10.1002/dneu.22546