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Mitochondria AND mTOR

Feng Ke, Jinqiang Yu, Wei Chen, Xiaomin Si, Xinhui Li, Fang Yang, Yingying Liao, Zhigang Zuo
Mitochondria has been identified as a promising target in several cancers. However, little is known on the effects of targeting mitochondria in retinoblastoma. In this work, we show that anti-malarial atovaquone, at clinically achievable concentration, demonstrates inhibitory effects to retinoblastoma cells, to a more extent than in normal retinal cells. Atovaquone also significantly increases chemosensitivity in retinoblastoma. Importantly, we show that retinoblastoma cells have higher level of mitochondrial respiration, membrane potential, mass and ATP compared to normal retinal cells...
June 11, 2018: Biochemical and Biophysical Research Communications
Ha Thi Vu, Masahiko Kobayashi, Ahmed M Hegazy, Yuko Tadokoro, Masaya Ueno, Atsuko Kasahara, Yusuke Takase, Naho Nomura, Hui Peng, Chiaki Ito, Yasushi Ino, Tomoki Todo, Mitsutoshi Nakada, Atsushi Hirao
Autophagy plays a critical role in tumorigenesis, but how autophagy contributes to cancer cells' responses to chemotherapeutics remains controversial. To investigate the roles of autophagy in malignant gliomas, we used CRISPR/CAS9 to knock out the ATG5 gene, which is essential for autophagosome formation, in tumor cells derived from glioblastoma patients. While ATG5 disruption inhibited autophagy, it did not change the phenotypes of glioma cells and did not alter their sensitivity to temozolomide, an agent used for glioblastoma patient therapy...
June 14, 2018: Cancer Science
Jiao Jiao Zhang, Xian Zhong Wang, Huynh Luong Do, Nisansala Chandimali, Tae Yoon Kang, Nameun Kim, Mrinmoy Ghosh, Sang Baek Lee, Young Sun Mok, Seong Bong Kim, Taeho Kwon, Dong Kee Jeong
Non-thermal plasma treatment is an emerging innovative technique with a wide range of biological applications. This study was conducted to investigate the effect of a non-thermal dielectric barrier discharge plasma technique on immature chicken Sertoli cell (SC) viability and the regulatory role of microRNA (miR)-7450. Results showed that plasma treatment increased SC apoptosis in a time- and dose-dependent manner. Plasma-induced SC apoptosis possibly resulted from the excess production of reactive oxygen species via the suppression of antioxidant defense systems and decreased cellular energy metabolism through the inhibition of adenosine triphosphate (ATP) release and respiratory enzyme activity in the mitochondria...
June 8, 2018: Scientific Reports
Yuehua Wei, Lulu Chen, Hui Xu, Conghua Xie, Yunfeng Zhou, Fuxiang Zhou
We investigated the relationship between significantly different genes of the mitochondria-to-nucleus retrograde signaling pathway (RTG) in H1299 ρ0 cells (mtDNA depleted cell) and compared their radiosensitivity to that of parental ρ+ cells, to determine the possible intervention targets of radiosensitization. ρ0 cells were depleted of mitochondrial DNA by chronic culturing in ethidium bromide at low concentration. Radiosensitivity was analyzed using clonogenic assay. Western blot was used to analyze the cell cycle-related proteins, serine/threonine kinase ataxia telangiectasia mutant (ATM), ataxia telangiectasia and Rad3-related protein (ATR) and cyclin B1 (CCNB1)...
June 4, 2018: Radiation Research
Tianren Wang, Elnur Babayev, Zongliang Jiang, Guangxin Li, Man Zhang, Ecem Esencan, Tamas Horvath, Emre Seli
Caseinolytic peptidase P mediates degradation of unfolded mitochondrial proteins and activates mitochondrial unfolded protein response (mtUPR) to maintain protein homeostasis. Clpp-/- female mice generate a lower number of mature oocytes and two-cell embryos, and no blastocysts. Clpp-/- oocytes have smaller mitochondria, with lower aspect ratio (length/width), and decreased expression of genes that promote fusion. A 4-fold increase in atretic follicles at 3 months, and reduced number of primordial follicles at 6-12 months are observed in Clpp-/- ovaries...
May 30, 2018: Aging Cell
Emmanuel Quansah, Wouter Peelaerts, J William Langston, David K Simon, Jerry Colca, Patrik Brundin
Several molecular pathways are currently being targeted in attempts to develop disease-modifying therapies to slow down neurodegeneration in Parkinson's disease. Failure of cellular energy metabolism has long been implicated in sporadic Parkinson's disease and recent research on rare inherited forms of Parkinson's disease have added further weight to the importance of energy metabolism in the disease pathogenesis. There exists a new class of anti-diabetic insulin sensitizers in development that inhibit the mitochondrial pyruvate carrier (MPC), a protein which mediates the import of pyruvate across the inner membrane of mitochondria...
May 24, 2018: Molecular Neurodegeneration
Jie Miao, Yacir Benomar, Sarah Al-Rifai, Ghislaine Poizat, Laure Riffault, Delphine Crepin, Mohammed Taouis
Autophagy is as a non-selective degradation pathway induced in energy-deprived cells and in non-starved cells by participating in cellular inflammatory responses mainly through the elimination of injured and aged mitochondria that constitute an important source of reactive oxygen species. We have previously reported that resistin/TLR4 signaling pathway induces inflammation and insulin resistance in neuronal cell. However, the impact of resistin-induced inflammation on neuronal autophagy is unknown. In the present study, we hypothesized that resistin-induced neuroinflammation could be attributed, at least partially, to the impairment of autophagy pathways in neuronal cells...
May 17, 2018: Journal of Endocrinology
Li Diao, Christopher Auger, Hisato Konoeda, Ali-Reza Sadri, Saeid Amini-Nik, Marc G Jeschke
Severely burned patients who are morbidly obese have poor clinical outcomes with aggravated metabolic consequences, a higher incidence of multiple organ dysfunction/failure, and significantly increased morbidity and mortality. The underlying mechanisms of these adverse outcomes are essentially unknown. Since the liver is one of the central metabolic organs, we hypothesized that thermal injury in obese patients leads to substantially increased lipolysis, hepatic fat infiltration, resulting in profound hepatic cellular and organellar alterations, consequently causing liver damage and severely augmented metabolic dysfunction...
May 10, 2018: Cell Death & Disease
Sindre Lee, Frode Norheim, Hanne L Gulseth, Torgrim M Langleite, Andreas Aker, Thomas E Gundersen, Torgeir Holen, Kåre I Birkeland, Christian A Drevon
Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) composition in skeletal muscle have been linked to insulin sensitivity. We evaluated the relationships between skeletal muscle PC:PE, physical exercise and insulin sensitivity. We performed lipidomics and measured PC and PE in m. vastus lateralis biopsies obtained from 13 normoglycemic normal weight men and 13 dysglycemic overweight men at rest, immediately after 45 min of cycling at 70% maximum oxygen uptake, and 2 h post-exercise, before as well as after 12 weeks of combined endurance- and strength-exercise intervention...
April 25, 2018: Scientific Reports
Joaquín G Cordero, Ramón García-Escudero, Jesús Avila, Ricardo Gargini, Vega García-Escudero
Alzheimer's disease is a proteinopathy characterized by accumulation of hyperphosphorylated Tau and β -amyloid. Autophagy is a physiological process by which aggregated proteins and damaged organelles are eliminated through lysosomal digestion. Autophagy deficiency has been demonstrated in Alzheimer's patients impairing effective elimination of aggregates and damaged mitochondria, leading to their accumulation, increasing their toxicity and oxidative stress. In the present study, we demonstrated by microarray analysis the downregulation of fundamental autophagy and mitophagy pathways in Alzheimer's patients...
2018: Oxidative Medicine and Cellular Longevity
Miguel Sanchez-Alvarez, Miguel Angel Del Pozo, Chris Bakal
A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
April 19, 2018: Scientific Reports
Xiaomin Yi, Limin Xiang, Yuying Huang, Yihai Wang, Xiangjiu He
BACKGROUND: Our previous study has revealed that the spirostanol saponins isolated from the rhizomes of Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) (Convallariaceae) (a reputed folk medicine) exhibited potent antiproliferative activity. However, the underlying mechanism of purified saponins remains unclear. More studies are necessary to assess the apoptosis and autophagy activities of the saponins from R. chinensis and clarify their antiproliferative mechanisms...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Fan Yang, Jianzhao Liao, Ruonan Pei, Wenlan Yu, Qingyue Han, Ying Li, Jianying Guo, Lianmei Hu, Jiaqiang Pan, Zhaoxin Tang
Copper (Cu) is an essential trace element that is required for the catalysis of several cellular enzymes. Excessive Cu could induce hepatotoxicity in humans and multiple animals. The purpose of this study was to investigate the effects of autophagy machinery on Cu-induced hepatotoxicity. Chicken hepatocytes were cultured in medium in the absence and presence of Cu sulfate (CuSO4 ) (0, 10, 50, and 100 μM) for 0, 6, 12, and 24 h, and in the combination of CuSO4 and N-acetyl-l-cysteine (NAC) (1 mM), rapamycin (10 nM), and 3-methyladenine (3-MA) (5 mM) for 24 h...
August 2018: Chemosphere
Ryan M Bradley, Darin Bloemberg, Juan J Aristizabal Henao, Ashkan Hashemi, Andrew S Mitchell, Val A Fajardo, Catherine Bellissimo, Emily B Mardian, Eric Bombardier, Marie-France Paré, Katherine A Moes, Ken D Stark, A Russell Tupling, Joe Quadrilatero, Robin E Duncan
Lysophosphatidic acid acyltransferase (LPAAT) δ/acylglycerophosphate acyltransferase 4 is a mitochondrial enzyme and one of five homologues that catalyze the acyl-CoA-dependent synthesis of phosphatidic acid (PA) from lysophosphatidic acid. We studied skeletal muscle LPAATδ and found highest levels in soleus, a red oxidative fibre-type that is rich in mitochondria, and lower levels in extensor digitorum longus (EDL) (white glycolytic) and gastrocnemius (mixed fibre-type). Using Lpaatδ-deficient mice, we found no change in soleus or EDL mass, or in treadmill time-to-exhaustion compared to wildtype littermates...
July 2018: Biochimica et Biophysica Acta
Mi Suk Choi, Sung-Min Moon, Seul Ah Lee, Bo-Ram Park, Jae-Sung Kim, Do Kyung Kim, Yong Hwan Kim, Chun Sung Kim
Adenosine has been identified to occur abundantly intra-and extracellularly, and to exert diverse biological functions, including the suppression of cell proliferation and the induction of apoptosis. Adenosine has been reported to induce apoptosis in several cancer cell lines; however, to the best of our knowledge, the effect of adenosine on head and neck cancer cells has not been investigated. Therefore, the purpose of the present study was to evaluate whether adenosine exerts any anticancer effect via induction of apoptosis in human pharyngeal squamous carcinoma FaDu cells...
May 2018: Oncology Letters
Li-Li Gong, Song Yang, Wen Zhang, Fei-Fei Han, Ya-Li Lv, Zi-Rui Wan, He Liu, Yang-Jie Jia, Ling-Ling Xuan, Li-Hong Liu
Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells...
April 2018: Journal of Pharmacological Sciences
Pau B Esparza-Moltó, José M Cuezva
Cancer cells reprogram energy metabolism by boosting aerobic glycolysis as a main pathway for the provision of metabolic energy and of precursors for anabolic purposes. Accordingly, the relative expression of the catalytic subunit of the mitochondrial H+ -ATP synthase-the core hub of oxidative phosphorylation-is downregulated in human carcinomas when compared with its expression in normal tissues. Moreover, some prevalent carcinomas also upregulate the ATPase inhibitory factor 1 (IF1), which is the physiological inhibitor of the H+ -ATP synthase...
2018: Frontiers in Oncology
Eun Jeong Jang, Sang Chan Kim, Ju-Hee Lee, Jong Rok Lee, Il Kon Kim, Su Youn Baek, Young Woo Kim
BACKGROUND: Laminaria japonica has frequently been used as a food supplement and drug in traditional oriental medicine. Among the major active constituents responsible for the bioactivities of L. japonica, fucoxanthin (FX) has been considered as a potential antioxidant. This study was conducted to examine the effects of L. japonica extract (LJE) or FX against oxidative stress on hepatocytes and to elucidate the overall their cellular mechanisms of the effects. METHODS: We constructed an in vitro model with the treatment of arachidonic acid (AA) + iron in HepG2 cells to stimulate the oxidative damage...
March 20, 2018: BMC Complementary and Alternative Medicine
Christine L Monteleon, Tanvir Agnihotri, Ankit Dahal, Mingen Liu, Vito W Rebecca, Gregory L Beatty, Ravi K Amaravadi, Todd W Ridky
Keratinocytes undergo significant structural remodeling during epidermal differentiation, including a broad transformation of the proteome coupled with a reduction in total cellular biomass. This suggests that intracellular digestion of proteins and organelles is necessary for keratinocyte differentiation. Here, we use both genetic and pharmacologic approaches to demonstrate that autophagy and lysosomal functions are required for keratinocyte differentiation in organotypic human skin. Lysosomal activity was required for mechanistic target of rapamycin signaling and mitochondrial oxidative metabolism...
March 9, 2018: Journal of Investigative Dermatology
Johann Schottler, Niklas Randoll, Ralph Lucius, Amke Caliebe, Johann Roider, Alexa Klettner
Anti-Vascular Endothelial Growth Factor (VEGF) therapy is given repeatedly for an extended period of time to patients when treated for age-related macular degeneration. While short-term effects of anti-VEGF agents on retinal pigment epithelial (RPE) cells have been investigated, the effects of long-term and repeated treatment on these cells are scarce. In this study, we have investigated the effects of anti-VEGF treatment after long-term, repeated treatment on cell aging and morphology. The experiments were conducted in primary porcine RPE cells passage one and two...
March 6, 2018: Experimental Eye Research
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