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Scientific Reports Aug 2016Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus... (Review)
Review
Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease.
Topics: Aged; Biopsy; DNA, Mitochondrial; Female; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Middle Aged; Mitochondria, Muscle; Mitochondrial Myopathies; Muscle, Skeletal; Mutation; Young Adult
PubMed: 27506553
DOI: 10.1038/srep30610 -
Mitochondrion May 2022Mitochondrial permeability transition pore (mPTP) is a channel that opens at the inner mitochondrial membrane under conditions of stress. Sirtuin 3 (Sirt3) is a... (Review)
Review
Mitochondrial permeability transition pore (mPTP) is a channel that opens at the inner mitochondrial membrane under conditions of stress. Sirtuin 3 (Sirt3) is a mitochondrial deacetylase known to play a major role in stress resistance and a regulatory role in cell death. This systematic review aims to elucidate the role of Sirt3 in mPTP inhibition. Electronic databases, including PubMed, EMBASE, Web of Science and Cochrane Library were searched up to May 2020. Original studies that investigated the relationship between Sirt3 and mPTP were included. Two reviewers independently extracted data on study characteristics, methods and outcomes. A total of 194 articles were found. Twenty-nine articles, which met criteria were included in the systematic review. Twenty-three studies provided evidence of the inhibitory effect of Sirt3 on the mPTP aperture. This review summarizes up-to-date evidence of the protective and inhibitory role of Sirt3 through deacetylating Cyclophilin D (CypD) on the mPTP aperture. Furthermore, we discuss the implications of this effect in disease.
Topics: Peptidyl-Prolyl Isomerase F; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Sirtuin 3
PubMed: 35346868
DOI: 10.1016/j.mito.2022.03.004 -
Nutrients Mar 2023Soy is rich in plant protein, isoflavones, and polyunsaturated fatty acids. To clarify the associations between soy intake and type 2 diabetes (T2D) and cardiovascular... (Meta-Analysis)
Meta-Analysis Review
Soy is rich in plant protein, isoflavones, and polyunsaturated fatty acids. To clarify the associations between soy intake and type 2 diabetes (T2D) and cardiovascular diseases (CVDs) events, we performed a meta-analysis and review. A total of 1963 studies met the inclusion criteria, and 29 articles with 16,521 T2D and 54,213 CVDs events were identified by the eligibility criteria. During a follow-up of 2.5-24 years, the risk of T2D, CVDs, coronary heart disease, and stroke in participants with the highest soy consumption decreased by 17% (total relative risk (TRR) = 0.83, 95% CI: 0.74-0.93), 13% (TRR = 0.87, 95% CI: 0.81-0.94), 21% (TRR = 0.79, 95% CI: 0.71-0.88), and 12% (TRR = 0.88, 95% CI: 0.79-0.99), respectively, compared to the lowest sot consumption. A daily intake of 26.7 g of tofu reduced CVDs risk by 18% (TRR = 0.82, 95% CI: 0.74-0.92) and 11.1 g of natto lowered the risk of CVDs by 17% (TRR = 0.83, 95% CI: 0.78-0.89), especially stroke. This meta-analysis demonstrated that soy consumption was negatively associated with the risks of T2D and CVDs and a specific quantity of soy products was the most beneficial for the prevention of T2D and CVDs. This study has been registered on PROSPERO (registration number: CRD42022360504).
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Risk; Soy Foods; Stroke; Risk Factors
PubMed: 36986086
DOI: 10.3390/nu15061358 -
Cancer Letters Feb 2024Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden.... (Review)
Review
Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden. Although chemotherapy is the most widely used treatment for cancer, its effectiveness is limited by drug resistance and severe side effects. Mitophagy is the principal mechanism that degrades damaged mitochondria via the autophagy/lysosome pathway to maintain mitochondrial homeostasis. Emerging evidence indicates that mitophagy plays crucial roles in tumorigenesis, particularly in cancer therapy. Mitophagy can exhibit dual effects in cancer, with both cancer-inhibiting or cancer-promoting function in a context-dependent manner. A variety of natural compounds have been found to affect cancer cell death and display anticancer properties by modulating mitophagy. In this review, we provide a systematic overview of mitophagy signaling pathways, and examine recent advances in the utilization of natural compounds for cancer therapy through the modulation of mitophagy. Furthermore, we address the inquiries and challenges associated with ongoing investigations concerning the application of natural compounds in cancer therapy based on mitophagy. Overcoming these limitations will provide opportunities to develop novel interventional strategies for cancer treatment.
Topics: Humans; Autophagy; Cell Death; Mitochondria; Mitophagy; Neoplasms
PubMed: 38097131
DOI: 10.1016/j.canlet.2023.216590 -
Developmental Neuroscience 2022Early life stress is commonly experienced by infants, especially preterm infants, and may impact their neurodevelopmental outcomes in their early and later lives.... (Review)
Review
Early life stress is commonly experienced by infants, especially preterm infants, and may impact their neurodevelopmental outcomes in their early and later lives. Mitochondrial function/dysfunction may play an important role underlying the linkage of prenatal and postnatal stress and neurodevelopmental outcomes in infants. This review aimed to provide insights on the relationship between early life stress and neurodevelopment and the mechanisms of mitochondrial function/dysfunction that contribute to the neuropathology of stress. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to develop this systematic review. PubMed, Scopus, PsycINFO, and Biosis databases were searched for primary research articles published between 2010 and 2021 that examined the relationships among mitochondrial function/dysfunction, infant stress, and neurodevelopment. Thirty studies were identified. There is evidence to support that mitochondrial function/dysfunction mediates the relationship between prenatal and postnatal stress and neurodevelopmental outcomes in infants. Maternal transgenerational transmission of mitochondrial bioenergetic patterns influenced prenatal stress induced neurodevelopmental outcomes and behavioral changes in infants. Multiple functionally relevant mitochondrial proteins, genes, and polymorphisms were associated with stress exposure. This is the first review of the role that mitochondrial function/dysfunction plays in the association between stress and neurodevelopmental outcomes in full-term and preterm infants. Although multiple limitations were found based on the lack of data on the influence of biological sex, and due to invasive sampling, and lack of longitudinal data, many genes and proteins associated with mitochondrial function/dysfunction were found to influence neurodevelopmental outcomes in the early life of infants.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Infant, Premature; Mitochondria; Stress, Physiological; Neurodevelopmental Disorders
PubMed: 35995037
DOI: 10.1159/000526491 -
Environmental Research Nov 2023Photothermal therapy (PTT) is an emerging non-invasive method used in cancer treatment. In PTT, near-infrared laser light is absorbed by a chromophore and converted into... (Review)
Review
Photothermal therapy (PTT) is an emerging non-invasive method used in cancer treatment. In PTT, near-infrared laser light is absorbed by a chromophore and converted into heat within the tumor tissue. PTT for cancer usually combines a variety of interactive plasmonic nanomaterials with laser irradiation. PTT enjoys PT agents with high conversion efficiency to convert light into heat to destroy malignant tissue. In this review, published studies concerned with the use of nanoparticles (NPs) in PTT were collected by a systematic and comprehensive search of PubMed, Cochrane, Embase, and Scopus databases. Gold, silver and iron NPs were the most frequent choice in PTT. The use of surface modified NPs allowed selective delivery and led to a precise controlled increase in the local temperature. The presence of NPs during PTT can increase the reactive generation of oxygen species, damage the DNA and mitochondria, leading to cancer cell death mainly via apoptosis. Many studies recently used core-shell metal NPs, and the effects of the polymer coating or ligands targeted to specific cellular receptors in order to increase PTT efficiency were often reported. The effective parameters (NP type, size, concentration, coated polymers or attached ligands, exposure conditions, cell line or type, and cell death mechanisms) were investigated individually. With the advances in chemical synthesis technology, NPs with different shapes, sizes, and coatings can be prepared with desirable properties, to achieve multimodal cancer treatment with precision and specificity.
PubMed: 37487920
DOI: 10.1016/j.envres.2023.116526 -
Mitochondrion Jan 2021Mitochondrial dysfunction is known to be associated with neurodegenerative diseases (NDDs), which is a major burden on the society. Therefore, understanding the...
Mitochondrial dysfunction is known to be associated with neurodegenerative diseases (NDDs), which is a major burden on the society. Therefore, understanding the regulation of mitochondrial dysfunctions and its implication in neurodegeneration has been major goal for exploiting these mechanisms to rescue neuronal death. The crosstalk between mitochondria and nucleus is important for different neuronal functions including axonal branching, energy homeostasis, neuroinflammation and neuronal survival. The decreased mitochondria capacity during progressive neurodegeneration leads to the altered OXPHOS activity and generation of ROS. The ROS levels in narrow physiological range can reprogram nuclear gene expression to enhance the cellular survival by phenomenon called mitohormesis. Here, we have systematically reviewed the existing reports of mitochondrial dysfunctions causing altered ROS levels in NDDs. We further discussed the role of ROS in regulating mitohormesis and emphasized the importance of mitohormesis in neuronal homeostasis. The emerging role of mitohormesis highlights its importance in future studies on intracellular ROS mediated rescue of mitochondrial dysfunction along with other prevailing mechanisms to alleviate neurodegeneration.
Topics: Cell Nucleus; Energy Metabolism; Gene Expression Regulation; Hormesis; Humans; Mitochondria; Neurodegenerative Diseases; Oxidative Phosphorylation; Reactive Oxygen Species
PubMed: 33220499
DOI: 10.1016/j.mito.2020.11.011 -
Therapeutic Advances in Gastroenterology Jan 2017Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder... (Review)
Review
Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy. Rare GI manifestations of MIDs include dry mouth, paradontosis, tracheoesophageal fistula, stenosis of the duodeno-jejunal junction, atresia or imperforate anus, liver cysts, pancreas lipomatosis, pancreatic cysts, congenital stenosis or obstruction of the GI tract, recurrent bowel perforations with intra-abdominal abscesses, postprandial abdominal pain, diverticulosis, or pneumatosis coli. Diagnosing GI involvement in MIDs is not at variance from diagnosing GI disorders due to other causes. Treatment of mitochondrial GI disease includes noninvasive or invasive measures. Therapy is usually symptomatic. Only for myo-neuro-gastro-intestinal encephalopathy is a causal therapy with autologous stem-cell transplantation available. It is concluded that GI manifestations of MIDs are more widespread than so far anticipated and that they must be recognized as early as possible to initiate appropriate diagnostic work-up and avoid any mitochondrion-toxic treatment.
PubMed: 28286566
DOI: 10.1177/1756283X16666806 -
Molecular Neurobiology Apr 2016Mitochondrial dysfunction has been reported to be involved in the pathophysiology of autism spectrum disorder (ASD). Studies investigating the possible association... (Meta-Analysis)
Meta-Analysis Review
Mitochondrial dysfunction has been reported to be involved in the pathophysiology of autism spectrum disorder (ASD). Studies investigating the possible association between ASD and polymorphism in SLC25A12, which encodes the mitochondrial aspartate/glutamate carrier, have yielded inconsistent results. We conducted a systematic review and meta-analysis of such studies to elucidate if and which SLC25A12 single nucleotide polymorphisms (SNPs) are associated with ASD. We searched PubMed, Ovid, Web of Science, and ERIC databases through September 20th, 2014. Odds ratios (ORs) were aggregated using random effect models. Sensitivity analyses were conducted based on study design (family-based or case-control). Fifteen out of 79 non-duplicate records were retained for qualitative synthesis. We pooled 10 datasets from 9 studies with 2001 families, 735 individuals with ASD and 632 typically developing (TD) individuals for the meta-analysis of rs2292813, as well as 11 datasets from 10 studies with 2016 families, 852 individuals with ASD and 1058 TD individuals for the meta-analysis of rs2056202. We found a statistically significant association between ASD and variant in rs2292813 (OR = 1.190, 95% CI 1.052-1.346, P = 0.006) as well as in rs2056202 (OR = 1.206, 95% CI 1.035-1.405, P = 0.016). Sensitivity analyses including only studies with family-based design demonstrated significant association between ASD and polymorphism in rs2292813 (OR = 1.216, 95% CI 1.075-1.376, P = 0.002) and rs2056202 (OR = 1.267, 95% CI 1.041-1.542, P = 0.018). In contrast, sensitivity analyses including case-control design studies only failed to find a significant association. Further research on the role of SLC25A12 and ASD may pave the way for potential innovative therapeutic interventions.
Topics: Autism Spectrum Disorder; Case-Control Studies; Datasets as Topic; Family Health; Genotype; Humans; Mitochondria; Mitochondrial Membrane Transport Proteins; Polymorphism, Single Nucleotide
PubMed: 25663199
DOI: 10.1007/s12035-015-9116-3 -
Pediatric Nephrology (Berlin, Germany) Jun 2023Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular... (Review)
Review
BACKGROUND
Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury.
METHODS
We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered.
RESULTS
For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-β-glucosaminidase, was often noted.
CONCLUSIONS
Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Humans; Valproic Acid; Kidney Tubules, Proximal; Kidney; Proteinuria; Epilepsy
PubMed: 36645492
DOI: 10.1007/s00467-022-05869-8