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mitochondrial biogenesis

Mitra Ansari Dezfouli, Maryam Zahmatkesh, Maryam Farahmandfar, Fariba Khodagholi
Melatonin has a potential therapeutic value in Alzheimer's disease (AD), a disease that is associated with a dramatic decline in memory and cognitive abilities. The aggregation of the amyloid β (Aβ) peptide, a hallmark of AD, deactivates mitochondrial biogenesis and antioxidant defenses. Melatonin as an endogenous antioxidant, decreases in plasma and cerebrospinal fluid of AD patients. Even though several experimental studies have demonstrated the melatonin neuroprotection in AD, clinical trials of melatonin therapy have not yet confirmed outstanding results in AD patients...
February 12, 2019: Physiology & Behavior
Ashley Mulcahy Toney, Rong Fan, Yibo Xian, Virginia Chaidez, Amanda E Ramer-Tait, Soonkyu Chung
OBJECTIVE: Urolithin A (UroA) is a major metabolite of ellagic acid produced following microbial catabolism in the gut. Emerging evidence has suggested that UroA modulates energy metabolism in various cells. However, UroA's physiological functions related to obesity and insulin resistance remain unclear. METHODS: Male mice were intraperitoneally administrated either UroA or dimethyl sulfoxide (vehicle) along with a high-fat diet for 12 weeks. Insulin sensitivity was evaluated via glucose and insulin tolerance tests and acute insulin signaling...
February 15, 2019: Obesity
Harold W Lee, Ella Baker, Kevin M Lee, Aaron Michael Persinger, William Hawkins, Melissa Puppa
Many forms of cancer are associated with loss of lean body mass, commonly attributed to decreased protein synthesis and stimulation of proteolytic pathways within the skeletal muscle. Leucine has been shown to improve protein synthesis, insulin signaling, and mitochondrial biogenesis, key signaling pathways influenced by tumor signaling. The purpose of this study was to examine the effects of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor bearing mice. Twenty male C57BL/6 mice were divided into four groups (n=5): Chow, leucine (Leu), Lewis lung carcinoma (LLC) implant, LLC+Leu...
February 15, 2019: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Luke W Thomas, Margaret Ashcroft
Oxygen is required for the survival of the majority of eukaryotic organisms, as it is important for many cellular processes. Eukaryotic cells utilize oxygen for the production of biochemical energy in the form of adenosine triphosphate (ATP) generated from the catabolism of carbon-rich fuels such as glucose, lipids and glutamine. The intracellular sites of oxygen consumption-coupled ATP production are the mitochondria, double-membraned organelles that provide a dynamic and multifaceted role in cell signalling and metabolism...
February 14, 2019: Cellular and Molecular Life Sciences: CMLS
Oluwaseun B Ogunbona, Steven M Claypool
The mitochondrial carrier family (MCF) is a group of transport proteins that are mostly localized to the inner mitochondrial membrane where they facilitate the movement of various solutes across the membrane. Although these carriers represent potential targets for therapeutic application and are repeatedly associated with human disease, research on the MCF has not progressed commensurate to their physiologic and pathophysiologic importance. Many of the 53 MCF members in humans are orphans and lack known transport substrates...
2019: Frontiers in Cell and Developmental Biology
Nunziata Maio, Ki Soon Kim, Gregory Holmes-Hampton, Anamika Singh, Tracey A Rouault
Loss-of-function mutations in the ABC transporter of the inner mitochondrial membrane, ABCB7, cause X-linked sideroblastic anemia with ataxia, a phenotype that remains largely unexplained by the proposed role of ABCB7 in exporting a special sulfur species for use in cytosolic iron-sulfur (Fe-S) cluster biogenesis. Here, we generated inducible ABCB7-knockdown cell lines to examine the time-dependent consequences of loss of ABCB7. We found that knockdown of ABCB7 led to significant loss of mitochondrial Fe-S proteins, which preceded the development of milder defects in cytosolic Fe-S enzymes...
February 14, 2019: Haematologica
Qiujun Yu, Yi-Yin Tai, Ying Tang, Jingsi Zhao, Vinny Negi, Miranda K Culley, Jyotsna Pilli, Wei Sun, Karin Brugger, Johannes Mayr, Rajeev Saggar, Rajan Saggar, W Dean Wallace, David J Ross, Aaron B Waxman, Stacy G Wendell, Steven J Mullett, John Sembrat, Mauricio Rojas, Omar F Khan, James E Dahlman, Masataka Sugahara, Nobuyuki Kagiyama, Taijyu Satoh, Manling Zhang, Ning Feng, John Gorcsan Iii, Sara O Vargas, Kathleen J Haley, Rahul Kumar, Brian B Graham, Robert Langer, Daniel G Anderson, Bing Wang, Sruti Shiva, Thomas Bertero, Stephen Y Chan
BACKGROUND: Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. The BolA Family Member 3 (BOLA3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined. METHODS: In vitro assessment of BOLA3 regulation and gain and loss of function assays were performed in human pulmonary artery endothelial cells (PAECs) using siRNA and lentiviral vectors expressing the mitochondrial isoform of BOLA3...
February 14, 2019: Circulation
Tina Toft Kristensen, Palle Lyngsie Pedersen, Jacob Larsen, Anne-Dorthe Feldthusen, Søren Jelstrup, Christina Ellervik
We have previously reported decreased thyroid function within the laboratory reference range and changes in mitochondrial function after hemithyroidectomy. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and coactivator-1β (PGC-1β) are key regulators of mitochondrial biogenesis and function. The aim was to examine the influence of hemithyroidectomy on the longitudinal change in mRNA expression of these genes. In addition, we measured longitudinal changes in mRNA expressions of the mitochoncrial-related genes nuclear factor erythroid-derived 2-like 2 (NFE2L2), mitochondrial transcription factor A (TFAM), and sodium dismutase 2 (SOD2)...
February 2019: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Sagnika Ghosh, Donna M Iadarola, Writoban Basu Ball, Vishal M Gohil
Barth syndrome (BTHS) is a rare multisystemic genetic disorder caused by mutations in the TAZ gene. TAZ encodes a mitochondrial enzyme that remodels the acyl chain composition of newly synthesized cardiolipin, a phospholipid unique to mitochondrial membranes. The clinical abnormalities observed in BTHS patients are caused by perturbations in various mitochondrial functions that rely on remodeled cardiolipin. However, the contribution of different cardiolipin-dependent mitochondrial functions to the pathology of BTHS is not fully understood...
February 11, 2019: IUBMB Life
Antoine H Chaanine, Lyle D Joyce, John M Stulak, Simon Maltais, David L Joyce, Joseph A Dearani, Katherine Klaus, K Sreekumaran Nair, Roger J Hajjar, Margaret M Redfield
BACKGROUND: The FOXO3a (forkhead box O3a)-BNIP3 (B-cell lymphoma 2/adenovirus E1B 19kDa interacting protein 3) pathway modulates mitochondrial dynamics and function and contributes to myocardial remodeling in rodent models of heart failure. We sought to investigate the expression of this pathway along with the expression of mitochondrial biogenesis (PGC-1α [peroxisome proliferator-activated receptor-γ coactivator-1α]), dynamics (DRP-1 [dynamin-related protein 1], OPA-1 [optic atrophy 1], and MFN 2 [mitofusin 2]), and oxidative phosphorylation (citrate synthase and electron transport chain complexes) markers and COX IV (cytochrome C oxidase) activity in myocardium from patients with valvular or ischemic heart disease and heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF)...
February 2019: Circulation. Heart Failure
Hripsimé Nahapetyan, Manon Moulis, Elisa Grousset, Julien Faccini, Marie-Hélène Grazide, Elodie Mucher, Meyer Elbaz, Wim Martinet, Cécile Vindis
Vascular smooth muscle cells (VSMCs) are one of the main cellular determinants in arterial pathology. A large body of evidence indicates that death of VSMCs is associated with features of high-risk/vulnerable atherosclerotic plaques. Mitochondrial turnover is an essential aspect of the mitochondrial quality control in which dysfunctional mitochondria are selectively eliminated through autophagy and replaced through expansion of preexisting mitochondria. Even though successful autophagy promotes VSMC survival, it is unclear whether reduced autophagic flux affects mitochondrial quality control of VSMCs in atherosclerotic plaques...
February 11, 2019: Cell Death & Disease
Mark A Lampert, Amabel M Orogo, Rita H Najor, Babette C Hammerling, Leonardo J Leon, Bingyan J Wang, Taeyong Kim, Mark A Sussman, Åsa B Gustafsson
Cell-based therapies represent a very promising strategy to repair and regenerate the injured heart to prevent progression to heart failure. To date, these therapies have had limited success due to a lack of survival and retention of the infused cells. Therefore, it is important to increase our understanding of the biology of these cells and utilize this information to enhance their survival and function in the injured heart. Mitochondria are critical for progenitor cell function and survival. Here, we demonstrate the importance of mitochondrial autophagy, or mitophagy, in the differentiation process in adult cardiac progenitor cells (CPCs)...
February 11, 2019: Autophagy
Désirée Schatton, Elena I Rugarli
Mitochondria are dynamic and plastic organelles, which flexibly adapt morphology, ATP production, and metabolic function to meet extrinsic challenges and demands. Regulation of mitochondrial biogenesis is essential during development and in adult life to survive stress and pathological insults, and is achieved not only by increasing mitochondrial mass, but also by remodeling the organellar proteome, metabolome, and lipidome. In the last decade, the post-transcriptional regulation of the expression of nuclear-encoded mitochondrial proteins has emerged as a fast, flexible, and powerful mechanism to shape mitochondrial function and coordinate it with other cellular processes...
December 2018: Critical Reviews in Biochemistry and Molecular Biology
Shibani Kanungo, Jacob Morton, Mekala Neelakantan, Kevin Ching, Jasmine Saeedian, Amy Goldstein
Primary mitochondrial disorders are a group of clinically variable and heterogeneous inborn errors of metabolism (IEMs), resulting from defects in cellular energy, and can affect every organ system of the body. Clinical presentations vary and may include symptoms of fatigue, skeletal muscle weakness, exercise intolerance, short stature, failure to thrive, blindness, ptosis and ophthalmoplegia, nystagmus, hearing loss, hypoglycemia, diabetes mellitus, learning difficulties, intellectual disability, seizures, stroke-like episodes, spasticity, dystonia, hypotonia, pain, neuropsychiatric symptoms, gastrointestinal reflux, dysmotility, gastrointestinal pseudo-obstruction, cardiomyopathy, cardiac conduction defects, and other endocrine, renal, cardiac, and liver problems...
December 2018: Annals of Translational Medicine
Meric A Altinoz, Aysel Ozpinar
The transcription factor, PPARδ is involved in suppressing inflammation, stimulating oligodendroglial biogenesis and myelination. Furthermore, activation of PPARδ directly protects mitochondria against noxious stimuli and stimulates biogenesis of new mitochondria. PPARδ activation directly inhibits neuronal cell death and reduces both the level and neurotoxicity of Amyloid-β fibers in Alzheimer's Disease (AD) models. Among the important ligands of PPARδ is erucic acid (EA, 22:1 n9), an edible omega-9 fatty acid and a component of Lorenzo's oil, which is used in the treatment of adrenoleukodystrophy (ALD)...
February 7, 2019: International Immunopharmacology
Zi-Xian Liu, Fang Dong, Sen Zhang, Ming-Zhe Han, Hideo Ema
Mitochondria are double-membrane organelles existing only in eukaryotic cells. Mitochondria perform various important functions,such as producing energy,regulating signal transduction,and contributing to stress response. Recent studies have highlighted an important role of mitochondria in the determination of hematopoietic stem cells (HSC) fate. Limited biogenesis or timely clearance of mitochondria is an important way against oxidative stress,which favors the quiescence of HSC. Accumulation of mitochondria may lead to proliferation of HSC,even the aging of HSC...
February 2019: Zhongguo Shi Yan Xue Ye Xue za Zhi
Hongfei Qiao, Xijing He, Qiaojun Zhang, Haifeng Yuan, Dong Wang, Libo Li, Yanping Hui, Zhonghen Wu, Wenjuan Li, Ni Zhang
After spinal cord injury, microglial cells are activated and converted to an M1 phenotype. Emerging evidence supports the hypothesis that glucose reprogramming accompanies microglial activation. What contributes to the activation of microglia and glucose reprogramming, however, remains unclear. In the current study, we investigated the role and underlying mechanism of a-synuclein in regulating the aerobic glycolysis in microglia. We found that a-synuclein contributed to the reprogramming of glucose metabolism in microglia by promoting glycolysis and inhibiting mitochondrial biogenesis and oxidative phosphorylation...
February 6, 2019: International Journal of Biological Macromolecules
Chihiro Kadooka, Kosuke Izumitsu, Masahira Onoue, Kayu Okutsu, Yumiko Yoshizaki, Kazunori Takamine, Masatoshi Goto, Hisanori Tamaki, Taiki Futagami
Aspergillus luchuensis mut . kawachii produces a large amount of citric acid during the process of fermenting shochu, a traditional Japanese distilled spirit. In this study, we characterized A. kawachii CtpA and YhmA, which are homologous to the yeast Saccharomyces cerevisiae mitochondrial citrate transporters Ctp1 and Yhm2, respectively. CtpA and YhmA were purified from A. kawachii and reconstituted into liposomes. The proteoliposomes exhibited only counter-exchange transport activity; CtpA transported citrate using counter substrates especially for cis -aconitate and malate, whereas YhmA transported citrate using a wider variety of counter substrates, including citrate, 2-oxoglutarate, malate, cis -aconitate, and succinate...
February 8, 2019: Applied and Environmental Microbiology
Robert B Bentham, Kevin Bryson, Gyorgy Szabadkai
Transcription of a large set of nuclear-encoded genes underlies biogenesis of mitochondria, regulated by a complex network of transcription factors and co-regulators. A remarkable heterogeneity can be detected in the expression of these genes in different cell types and tissues, and the recent availability of large gene expression compendiums allows the quantification of specific mitochondrial biogenesis patterns. We have developed a method to effectively perform this task. Massively correlated biclustering (MCbiclust) is a novel bioinformatics method that has been successfully applied to identify co-regulation patterns in large genesets, underlying essential cellular functions and determining cell types...
2019: Methods in Molecular Biology
Raquel L Bernardino, Tânia R Dias, Bruno P Moreira, Mariana Cunha, Alberto Barros, Elsa Oliveira, Mário Sousa, Marco G Alves, Pedro F Oliveira
The process that allows cells to control their pH and bicarbonate levels is essential for ionic and metabolic equilibrium. Carbonic anhydrases (CAs) catalyse the conversion of CO2 to HCO3 - and H+ and are thus essential for this process. Herein, we inhibited CAs with acetazolamide - ACT and SLC-0111 - to study their involvement in the metabolism, mitochondrial potential, mitochondrial biogenesis and lipid metabolism of human Sertoli cells (hSCs), obtained from biopsies from men with conserved spermatogenesis...
February 6, 2019: FEBS Journal
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