Read by QxMD icon Read

OXPHOS disease

Corina T Madreiter-Sokolowski, Armin A Sokolowski, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS) ensures a supply of adenosine triphosphate (ATP), but is also the main source of potentially harmful levels of reactive oxygen species (ROS)...
March 16, 2018: Genes
Lotte Kors, Elena Rampanelli, Geurt Stokman, Loes Butter, Ntsiki M Held, Nike Claessen, Per W B Larsen, Joanne Verheij, Coert J Zuurbier, Gerhard Liebisch, Gerd Schmitz, Stephen E Girardin, Sandrine Florquin, Riekelt H Houtkooper, Jaklien C Leemans
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction...
March 4, 2018: Biochimica et Biophysica Acta
Chao-Pin Hsiao, Charles Hoppel
Mitochondrial oxidative phosphorylation (OXPHOS) is responsible for producing most of the adenosine triphosphate required by eukaryotic cells. Lymphocytes make up the majority of the peripheral blood mononuclear cells. Peripheral blood mononuclear cells are readily obtainable, providing an ideal sample to monitor systemic changes and understand molecular signaling mechanisms in disease processes. Mitochondrial energy metabolism of lymphocyte has been used to screen for OXPHOS disorders. While there are increasing studies of lymphocyte OXPHOS, few studies examined activity of electron transport chain of lymphocyte mitochondria...
March 2, 2018: Analytical Biochemistry
R Stinkens, B W van der Kolk, J Jordan, T Jax, S Engeli, T Heise, J W Jocken, M May, C Schindler, B Havekes, N Schaper, D Albrecht, S Kaiser, N Hartmann, M Letzkus, T H Langenickel, G H Goossens, E E Blaak
Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients...
March 2, 2018: Scientific Reports
Guillaume Geffroy, Rayane Benyahia, Samuel Frey, Valerie Desquiret-Dumas, Naig Gueguen, Celine Bris, Sophie Belal, Aurore Inisan, Aurelie Renaud, Arnaud Chevrollier, Daniel Henrion, Dominique Bonneau, Franck Letournel, Guy Lenaers, Pascal Reynier, Vincent Procaccio
Ketogenic diet (KD) which combined carbohydrate restriction and the addition of ketone bodies has emerged as an alternative metabolic intervention used as an anticonvulsant therapy or to treat different types of neurological or mitochondrial disorders including MELAS syndrome. MELAS syndrome is a severe mitochondrial disease mainly due to the m.3243A > G mitochondrial DNA mutation. The broad success of KD is due to multiple beneficial mechanisms with distinct effects of very low carbohydrates and ketones...
February 14, 2018: Biochimica et Biophysica Acta
Rick Kamps, Radek Szklarczyk, Tom E Theunissen, Debby M E I Hellebrekers, Suzanne C E H Sallevelt, Iris B Boesten, Bart de Koning, Bianca J van den Bosch, Gajja S Salomons, Marisa Simas-Mendes, Rob Verdijk, Kees Schoonderwoerd, Irenaeus F M de Coo, Jo M Vanoevelen, Hubert J M Smeets
This study aims to identify gene defects in pediatric cardiomyopathy and early-onset brain disease with oxidative phosphorylation (OXPHOS) deficiencies. We applied whole-exome sequencing in three patients with pediatric cardiomyopathy and early-onset brain disease with OXPHOS deficiencies. The brain pathology was studied by MRI analysis. In consanguineous patient 1, we identified a homozygous intronic variant (c.850-3A > G) in the QRSL1 gene, which was predicted to cause abnormal splicing. The variant segregated with the disease and affected the protein function, which was confirmed by complementation studies, restoring OXPHOS function only with wild-type QRSL1...
February 13, 2018: European Journal of Human Genetics: EJHG
Maximilian Pohland, Maren Pellowska, Heike Asseburg, Stephanie Hagl, Martina Reutzel, Aljoscha Joppe, Dirk Berressem, Schamim H Eckert, Mario Wurglics, Manfred Schubert-Zsilavecz, Gunter P Eckert
BACKGROUND: Current approved drugs for Alzheimer's disease (AD) only attenuate symptoms, but do not cure the disease. The pirinixic acid derivate MH84 has been characterized as a dual gamma-secretase/proliferator activated receptor gamma (PPARγ) modulator in vitro. Pharmacokinetic studies in mice showed that MH84 is bioavailable after oral administration and reaches the brain. We recently demonstrated that MH84 improved mitochondrial dysfunction in a cellular model of AD. In the present study, we extended the pharmacological characterization of MH84 to 3-month-old Thy-1 AβPPSL mice (harboring the Swedish and London mutation in human amyloid precursor protein (APP)) which are characterized by enhanced AβPP processing and cerebral mitochondrial dysfunction, representing a mouse model of early AD...
February 13, 2018: Alzheimer's Research & Therapy
Bodil Bjørndal, Eva Katrine Alterås, Carine Lindquist, Asbjørn Svardal, Jon Skorve, Rolf K Berge
Background: The 4-thia fatty acid tetradecylthiopropionic acid (TTP) is known to inhibit mitochondrial β-oxidation, and can be used as chemically induced hepatic steatosis-model in rodents, while 3-thia fatty acid tetradecylthioacetic acid (TTA) stimulates fatty acid oxidation through activation of peroxisome proliferator activated receptor alpha (PPARα). We wished to determine how these two compounds affected in vivo respiration and mitochondrial efficiency, with an additional goal to elucidate whether mitochondrial function is reflected in plasma acylcarnitine levels...
2018: Nutrition & Metabolism
André F Camargo, Marina M Chioda, Ana P C Rodrigues, Geovana S Garcia, Emily A McKinney, Howard T Jacobs, Marcos T Oliveira
The mitochondrial respiratory chain in vertebrates and arthropods is different from that of most other eukaryotes because they lack alternative enzymes that provide electron transfer pathways additional to the oxidative phosphorylation (OXPHOS) system. However, the use of diverse experimental models, such as human cells in culture, Drosophila melanogaster and the mouse, has demonstrated that the transgenic expression of these alternative enzymes can impact positively many phenotypes associated with human mitochondrial and other cellular dysfunction, including those typically presented in complex IV deficiencies, Parkinson's, and Alzheimer's...
January 31, 2018: Cell Biology International
Karina Salvador-Severo, Leopoldo Gómez-Caudillo, Héctor Quezada, José de Jesús García-Trejo, Alan Cárdenas-Conejo, Martha Elisa Vázquez-Memije, Fernando Minauro-Sanmiguel
BACKGROUND: Mitochondriopathies are multisystem diseases affecting the oxidative phosphorylation (OXPHOS) system. Skin fibroblasts are a good model for the study of these diseases. Fibroblasts with a complex IV mitochondriopathy were used to determine the molecular mechanism and the main affected functions in this disease. METHODS: Skin fibroblast were grown to assure disease phenotype. Mitochondria were isolated from these cells and their proteome extracted for protein identification...
May 2017: Boletín Médico del Hospital Infantil de México
Madhavika N Serasinghe, Jesse D Gelles, Kent Li, Lauren Zhao, Franco Abbate, Marie Syku, Jarvier N Mohammed, Brateil Badal, Cuahutlehuanitzin A Rangel, Kyle L Hoehn, Julide Tok Celebi, Jerry Edward Chipuk
Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in treating melanoma, but are unsuccessful in achieving long-term remission. Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or Trametinib, respectively. Consequently, exposure to these therapies reprograms cellular metabolism to increase mitochondrial respiration and restrain cell death commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is the major site of anti-apoptotic BCL-2 protein function, we hypothesized that suppressing these critical mitochondrial membrane functions would be a rational approach to maximize the pro-apoptotic effect of MAPK inhibition...
January 18, 2018: Cell Death & Disease
Elena Herbers, Nina J Kekäläinen, Anu Hangas, Jaakko L Pohjoismäki, Steffi Goffart
The different cell types of multicellular organisms have specialized physiological requirements, affecting also their mitochondrial energy production and metabolism. The genome of mitochondria is essential for mitochondrial oxidative phosphorylation (OXHPOS) and thus plays a central role in many human mitochondrial pathologies. Disorders affecting mitochondrial DNA (mtDNA) maintenance are typically resulting in a tissue-specific pattern of mtDNA deletions and rearrangements. Despite this role in disease as well as a biomarker of mitochondrial biogenesis, the tissue-specific parameters of mitochondrial DNA maintenance have been virtually unexplored...
January 12, 2018: Mitochondrion
Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
Sze Chern Lim, Makiko Tajika, Masaru Shimura, Kirstyn T Carey, David A Stroud, Kei Murayama, Akira Ohtake, Matthew McKenzie
Medium-chain acyl-Coenzyme A dehydrogenase (MCAD) is involved in the initial step of mitochondrial fatty acid β-oxidation (FAO). Loss of function results in MCAD deficiency, a disorder that usually presents in childhood with hypoketotic hypoglycemia, vomiting and lethargy. While the disruption of mitochondrial fatty acid metabolism is the primary metabolic defect, secondary defects in mitochondrial oxidative phosphorylation (OXPHOS) may also contribute to disease pathogenesis. Therefore, we examined OXPHOS activity and stability in MCAD-deficient patient fibroblasts that have no detectable MCAD protein...
January 9, 2018: Scientific Reports
Francesco Bruni, Ivano Di Meo, Emanuele Bellacchio, Bryn D Webb, Robert McFarland, Zofia M A Chrzanowska-Lightowlers, Langping He, Ewa Skorupa, Isabella Moroni, Anna Ardissone, Anna Walczak, Henna Tyynismaa, Pirjo Isohanni, Hanna Mandel, Holger Prokisch, Tobias Haack, Penelope E Bonnen, Bertini Enrico, Ewa Pronicka, Daniele Ghezzi, Robert W Taylor, Daria Diodato
In recent years, an increasing number of mitochondrial disorders have been associated with mutations in mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs), which are key enzymes of mitochondrial protein synthesis. Bi-allelic functional variants in VARS2, encoding the mitochondrial valyl tRNA-synthetase, were first reported in a patient with psychomotor delay and epilepsia partialis continua associated with an oxidative phosphorylation (OXPHOS) complex I defect, before being described in a patient with a neonatal form of encephalocardiomyopathy...
January 3, 2018: Human Mutation
Jiancheng Wang, Yinong Huang, Jianye Cai, Qiong Ke, Jiaqi Xiao, Weijun Huang, Hongyu Li, Yuan Qiu, Yi Wang, Bin Zhang, Haoxiang Wu, Yanan Zhang, Xin Sui, Adham Sameer A Bardeesi, Andy Peng Xiang
Neural stem/progenitor cells (NSPCs) transplantation provides an alternative approach for various central nervous system (CNS) diseases treatment, while the difficulties in NSPC acquisition and expansion limit their further application. Unveiling the mechanism of NSPC stemness regulation may contribute to its further application. Nestin, generally recognized as a marker of NSPCs, plays a crucial role in the CNS development and NSPC stemness maintenance. Here, we report that Nestin loss triggers mitochondrial network remodeling and enhances oxidative phosphorylation (OXPHOS) in NSPCs treated with Nestin RNA interference (RNAi)...
January 3, 2018: Stem Cells
Paul V Sabatini, Thilo Speckmann, Cuilan Nian, Maria M Glavas, Chi Kin Wong, Ji Soo Yoon, Tatsuya Kin, A M James Shapiro, William T Gibson, C Bruce Verchere, Francis C Lynn
Depolarization of neuroendocrine cells results in calcium influx, which induces vesicle exocytosis and alters gene expression. These processes, along with the restoration of resting membrane potential, are energy intensive. We hypothesized that cellular mechanisms exist to maximize energy production during excitation. Here, we demonstrate that NPAS4, an immediate early basic helix-loop-helix (bHLH)-PAS transcription factor, acts to maximize energy production by suppressing hypoxia-inducible factor 1α (HIF1α)...
January 2, 2018: Cell Reports
Nadee Nissanka, Carlos T Moraes
Mitochondria are essential organelles within the cell where most ATP is produced through oxidative phosphorylation (OXPHOS). A subset of the genes needed for this process are encoded by the mitochondrial DNA (mtDNA). One consequence of OXPHOS is the production of mitochondrial reactive oxygen species (ROS), whose role in mediating cellular damage, particularly in damaging mtDNA during aging, has been controversial. There are subsets of neurons that appear to be more sensitive to ROS-induced damage, and mitochondrial dysfunction has been associated with several neurodegenerative disorders...
December 27, 2017: FEBS Letters
Lekha Mikkilineni, Diana Whitaker-Menezes, Marina Domingo-Vidal, John Sprandio, Paola Avena, Paolo Cotzia, Alina Dulau-Florea, Jerald Gong, Guldeep Uppal, Tingting Zhan, Benjamin Leiby, Zhao Lin, Barbara Pro, Federica Sotgia, Michael P Lisanti, Ubaldo Martinez-Outschoorn
BACKGROUND: Twenty percent of patients with classical Hodgkin Lymphoma (cHL) have aggressive disease defined as relapsed or refractory disease to initial therapy. At present we cannot identify these patients pre-treatment. The microenvironment is very important in cHL because non-cancer cells constitute the majority of the cells in these tumors. Non-cancer intra-tumoral cells, such as tumor-associated macrophages (TAMs) have been shown to promote tumor growth in cHL via crosstalk with the cancer cells...
June 2017: Seminars in Oncology
Raouia Ghorbel, Ghada Ben Salah, Rania Ghorbel, Afif Ben Mahmoud, Imen Chamkha, Emna Mkaouar-Rebai, Leila Ammar-Keskes, Faiza Fakhfakh
Mitochondria play an essential role to supply the cell with metabolic energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As a consequence, they are also the primary source of cellular reactive oxygen species (ROS) which can cause oxidative damage of individual respiratory chain complexes. Indeed, affected OXPHOS subunits result in decreases in ATP production and increases in ROS formation which generate oxidative phosphorylation deficiency leading to mitochondrial dysfunctions...
December 12, 2017: Environmental Science and Pollution Research International
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"