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https://www.readbyqxmd.com/read/28448495/dysregulation-of-inf2-mediated-mitochondrial-fission-in-spop-mutated-prostate-cancer
#1
Xiaofeng Jin, Jie Wang, Kun Gao, Pingzhao Zhang, Longfang Yao, Yan Tang, Lisha Tang, Jian Ma, Jiantao Xiao, Enceng Zhang, Jie Zhu, Bin Zhang, Shi-Min Zhao, Yao Li, Shancheng Ren, Haojie Huang, Long Yu, Chenji Wang
Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alternations. SPOP (Speckle-type POZ Protein) was one of the most frequently mutated genes in primary prostate cancer, suggesting SPOP is a potential driver of prostate cancer development and progression. However, how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation...
April 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28446709/control-of-mitochondrial-biogenesis-and-function-by-the-ubiquitin-proteasome-system
#2
REVIEW
Piotr Bragoszewski, Michal Turek, Agnieszka Chacinska
Mitochondria are pivotal organelles in eukaryotic cells. The complex proteome of mitochondria comprises proteins that are encoded by nuclear and mitochondrial genomes. The biogenesis of mitochondrial proteins requires their transport in an unfolded state with a high risk of misfolding. The mislocalization of mitochondrial proteins is deleterious to the cell. The electron transport chain in mitochondria is a source of reactive oxygen species that damage proteins. Mitochondrial dysfunction is linked to many pathological conditions and, together with the loss of cellular protein homeostasis (proteostasis), are hallmarks of ageing and ageing-related degeneration diseases...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28444922/regulation-of-organelle-function-by-metformin
#3
REVIEW
Jeongho Kim, Young-Jai You
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs...
April 26, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28444733/hybridization-increases-mitochondrial-production-of-reactive-oxygen-species-in-sunfish
#4
Sherry N N Du, Fariborz Khajali, Neal J Dawson, Graham R Scott
Mitochondrial dysfunction and oxidative stress have been suggested to be possible mechanisms underlying hybrid breakdown, as a result of mito-nuclear incompatibilities in respiratory complexes of the electron transport system. However, it remains unclear whether hybridization increases the production of reactive oxygen species (ROS) by mitochondria. We used high-resolution respirometry and fluorometry on isolated liver mitochondria to examine mitochondrial physiology and ROS emission in naturally occurring hybrids of pumpkinseed (Lepomis gibbosus) and bluegill (L...
April 26, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28444389/smithrnas-could-mitochondria-bend-nuclear-regulation
#5
Andrea Pozzi, Federico Plazzi, Liliana Milani, Fabrizio Ghiselli, Marco Passamonti
Typically, animal mitochondria have very compact genomes, with few short intergenic regions, and no introns. Hence, it may seem that there is little space for unknown functions in mitochondrial DNA (mtDNA). However, mtDNA can also operate through RNA interference, as small non coding RNAs (sncRNAs) produced by mtDNA have already been proposed for humans. We sequenced sncRNA libraries from isolated mitochondria of Ruditapes philippinarum (Mollusca Bivalvia) gonads, a species with doubly uniparental inheritance of mitochondria (DUI), and identified several putative sncRNAs of mitochondrial origin...
April 21, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28444329/the-eye-drop-preservative-benzalkonium-chloride-potently-induces-mitochondrial-dysfunction-and-preferentially-affects-lhon-mutant-cells
#6
Sandipan Datta, Christophe Baudouin, Francoise Brignole-Baudouin, Alexandre Denoyer, Gino A Cortopassi
Purpose: Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Method: Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28442745/phosphorylation-of-the-mitochondrial-autophagy-receptor-nix-enhances-its-interaction-with-lc3-proteins
#7
Vladimir V Rogov, Hironori Suzuki, Mija Marinković, Verena Lang, Ryuichi Kato, Masato Kawasaki, Maja Buljubašić, Matilda Šprung, Natalia Rogova, Soichi Wakatsuki, Anne Hamacher-Brady, Volker Dötsch, Ivan Dikic, Nathan R Brady, Ivana Novak
The mitophagy receptor Nix interacts with LC3/GABARAP proteins, targeting mitochondria into autophagosomes for degradation. Here we present evidence for phosphorylation-driven regulation of the Nix:LC3B interaction. Isothermal titration calorimetry and NMR indicate a ~100 fold enhanced affinity of the serine 34/35-phosphorylated Nix LC3-interacting region (LIR) to LC3B and formation of a very rigid complex compared to the non-phosphorylated sequence. Moreover, the crystal structure of LC3B in complex with the Nix LIR peptide containing glutamic acids as phosphomimetic residues and NMR experiments revealed that LIR phosphorylation stabilizes the Nix:LC3B complex via formation of two additional hydrogen bonds between phosphorylated serines of Nix LIR and Arg11, Lys49 and Lys51 in LC3B...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442536/tango1-recruits-sec16-to-coordinately-organize-er-exit-sites-for-efficient-secretion
#8
Miharu Maeda, Toshiaki Katada, Kota Saito
Mammalian endoplasmic reticulum (ER) exit sites export a variety of cargo molecules including oversized cargoes such as collagens. However, the mechanisms of their assembly and organization are not fully understood. TANGO1L is characterized as a collagen receptor, but the function of TANGO1S remains to be investigated. Here, we show that direct interaction between both isoforms of TANGO1 and Sec16 is not only important for their correct localization but also critical for the organization of ER exit sites. The depletion of TANGO1 disassembles COPII components as well as membrane-bound ER-resident complexes, resulting in fewer functional ER exit sites and delayed secretion...
April 25, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28442351/major-depressive-disorder-mediates-accelerated-aging-in-rats-subjected-to-chronic-mild-stress
#9
Xiaoxian Xie, Yangyang Chen, Lingyan Ma, Qichen Shen, Liangfeng Huang, Binggong Zhao, Tao Wu, Zhengwei Fu
Major depressive disorder (MDD) has a complex etiology and is characterized by a change in mood and psychophysiological state. MDD has been shown to mediate accelerated biological aging in patients, although the underlying mechanism is not well understood. In the present study, we used a chronic mild stress (CMS) paradigm to induce anhedonia, one of the main symptoms of MDD. CMS induced depression-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swim test...
April 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28442347/chronic-mitochondrial-calcium-elevation-suppresses-leaf-senescence
#10
Shijuan Fu, Luhua Li, Huimin Kang, Xue Yang, Shuzhen Men, Yuequan Shen
Mitochondria Ca(2+) overload has long been recognized as a cell death trigger. Unexpectedly, we demonstrated a signaling complex composed of Calmodulin (CaM), Arabidopsis thaliana Bcl-2-associated athanogene 5 (AtBAG5) and Heat-shock cognate 70 protein (Hsc70) within Arabidopsis thaliana mitochondria which transduces mitochondria Ca(2+) elevations to suppress leaf senescence. Gain- and loss-of-function AtBAG5 mutant plants revealed that, mitochondria Ca(2+) elevation significantly increase chlorophyll retention and decrease H2O2 level in dark-induced leaf senescence assay...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28442211/leigh-like-neuroimaging-features-associated-with-new-biallelic-mutations-in-opa1
#11
Anna Rubegni, Tiziana Pisano, Giacomo Bacci, Alessandra Tessa, Roberta Battini, Elena Procopio, Sabrina Giglio, Rosa Pasquariello, Filippo Maria Santorelli, Renzo Guerrini, Claudia Nesti
Behr syndrome is characterized by the association of early onset optic atrophy, cerebellar ataxia, pyramidal signs, peripheral neuropathy and mental retardation. Recently, some cases were reported to be caused by biallelic mutations in OPA1. We describe an 11-year-old girl (Pt1) and a 7-year-old boy (Pt2) with cognitive delay, ataxic gait and clinical signs suggestive of a peripheral neuropathy, with onset in early infancy. In Pt1 ocular fundus examination revealed optic disk pallor whereas Pt2 exhibited severe optic atrophy...
April 15, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28441756/the-interactions-between-zno-nanoparticles-nps-and-%C3%AE-linolenic-acid-lna-complexed-to-bsa-did-not-influence-the-toxicity-of-zno-nps-on-hepg2-cells
#12
Yiwei Zhou, Xin Fang, Yu Gong, Aiping Xiao, Yixi Xie, Liangliang Liu, Yi Cao
BACKGROUND: Nanoparticles (NPs) entering the biological environment could interact with biomolecules, but little is known about the interaction between unsaturated fatty acids (UFA) and NPs. METHODS: This study used α-linolenic acid (LNA) complexed to bovine serum albumin (BSA) for UFA and HepG2 cells for hepatocytes. The interactions between BSA or LNA and ZnO NPs were studied. RESULTS: The presence of BSA or LNA affected the hydrodynamic size, zeta potential, UV-Vis, fluorescence, and synchronous fluorescence spectra of ZnO NPs, which indicated an interaction between BSA or LNA and NPs...
April 24, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28440085/actinomycin-d-synergistically-enhances-the-cytotoxicity-of-cddp-on-kb-cells-by-activating-p53-via-decreasing-p53-mdm2-complex
#13
Lin Wang, Xiao-Cong Pang, Zi-Ru Yu, Sheng-Qian Yang, Ai-Lin Liu, Jin-Hua Wang, Guan-Hua Du
The aim of this study is to investigate the synergism of low dose of actinomycin D (LDActD) to the cytotoxicity of cisplatin (CDDP) on KB cells. The role of P53 reactivation by LDActD in the synergism and its mechanism were further studied. Cell viability was determined by MTT assay. Apoptosis was determined by AnnexinV-FITC/PI staining. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Expression of proteins was detected by Western blotting (WB) and/or immunofluorescence (IF). Molecular docking of actinomycin D (ACTD) to Mouse double minute 2 homolog (MDM2) and Mouse double minute 2 homolog X (MDMX)...
April 25, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28439028/bgp-15-prevents-the-death-of-neurons-in-a-mouse-model-of-familial-dysautonomia
#14
Sarah B Ohlen, Magdalena L Russell, Michael J Brownstein, Frances Lefcort
Hereditary sensory and autonomic neuropathy type III, or familial dysautonomia [FD; Online Mendelian Inheritance in Man (OMIM) 223900], affects the development and long-term viability of neurons in the peripheral nervous system (PNS) and retina. FD is caused by a point mutation in the gene IKBKAP/ELP1 that results in a tissue-specific reduction of the IKAP/ELP1 protein, a subunit of the Elongator complex. Hallmarks of the disease include vasomotor and cardiovascular instability and diminished pain and temperature sensation caused by reductions in sensory and autonomic neurons...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438176/the-pink1-p-i368n-mutation-affects-protein-stability-and-ubiquitin-kinase-activity
#15
Maya Ando, Fabienne C Fiesel, Roman Hudec, Thomas R Caulfield, Kotaro Ogaki, Paulina Górka-Skoczylas, Dariusz Koziorowski, Andrzej Friedman, Li Chen, Valina L Dawson, Ted M Dawson, Guojun Bu, Owen A Ross, Zbigniew K Wszolek, Wolfdieter Springer
BACKGROUND: Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson's disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degradation in order to prevent their accumulation and eventually cell death. Homozygous or compound heterozygous loss of either gene function disrupts this protective pathway, though at different steps and by distinct mechanisms...
April 24, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28436948/mitochondrial-elongation-mediated-glucose-metabolism-reprogramming-is-essential-for-tumour-cell-survival-during-energy-stress
#16
J Li, Q Huang, X Long, X Guo, X Sun, X Jin, Z Li, T Ren, P Yuan, X Huang, H Zhang, J Xing
To date, mechanisms of tumour cell survival under energy stress are not well understood. Cumulative evidence is beginning to reveal that specific mitochondrial morphologies are often associated with energetic states and survival of cells. However, the functional roles of mitochondria in the metabolic adaptation of tumour cells to energy stress remain to be elucidated. In this study, we first investigated the changes in mitochondrial morphology induced by nutrition deprivation in tumour cells, and the underlying molecular mechanism...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436418/oxoaporphine-metal-complexes-co-ii-ni-ii-zn-ii-with-high-antitumor-activity-by-inducing-mitochondria-mediated-apoptosis-and-s-phase-arrest-in-hepg2
#17
Jiao-Lan Qin, Wen-Ying Shen, Zhen-Feng Chen, Li-Fang Zhao, Qi-Pin Qin, Yan-Cheng Yu, Hong Liang
Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1-3 have been synthesized and fully characterized. 1-3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1-3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80-3 and SK-OV-3/DDP cells, with IC50 value of 0.23-4.31 μM. Interestingly, 0.5 μM 1-3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435050/the-human-krebs-cycle-2-oxoglutarate-dehydrogenase-complex-creates-an-additional-source-of-superoxide-hydrogen-peroxide-from-2-oxoadipate-as-alternative-substrate
#18
Natalia S Nemeria, Gary Gerfen, Elena Guevara, Pradeep Reddy Nareddy, Michal Szostak, Frank Jordan
Recently, we reported that the human 2-oxoglutarate dehydrogenase (hE1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHc) could produce the reactive oxygen species superoxide and hydrogen peroxide (detected by chemical means) from its substrate 2-oxoglutarate (OG), most likely concurrently with one-electron oxidation by dioxygen of the thiamin diphosphate (ThDP)-derived enamine intermediate to a C2α-centered radical (detected by Electron Paramagnetic Resonance) [Nemeria et al., 2014; Ambrus et al...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28434671/resveratrol-improves-mitochondrial-function-in-the-remnant-kidney-from-5-6-nephrectomized-rats
#19
Yan Hui, Miaomiao Lu, Yarong Han, Hongli Zhou, Wei Liu, Lijing Li, Ruixia Jin
Mitochondrial dysfunction is involved in the pathogenesis of chronic kidney disease (CKD). Resveratrol has been demonstrated to be beneficial for the recovery of kidney diseases. In this study, the 5/6 nephrectomized rat was used as a CKD model and the TGF-β1-exposed mouse mesangial cells were used as an in vitro model. Pathological examination showed that resveratrol treatment attenuated glomerular injury in the remnant kidney of 5/6 nephrectomized rat. Additionally, resveratrol improved mitochondrial function in vivo and in vitro, as evidenced by increasing mitochondrial membrane potential, increasing ATP, decreasing reactive oxygen species production and enhancing activities of complex I and III...
April 20, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28434121/intracellular-position-of-mitochondria-in-mesophyll-cells-differs-between-c3-and-c4-grasses
#20
Yuto Hatakeyama, Osamu Ueno
In C3 plants, part of the CO2 fixed during photosynthesis in chloroplasts is released from mitochondria during photorespiration by decarboxylation of glycine via glycine decarboxylase (GDC), thereby reducing photosynthetic efficiency. The apparent positioning of most mitochondria in the interior (vacuole side of chloroplasts) of mesophyll cells in C3 grasses would increase the efficiency of refixation of CO2 released from mitochondria by ribulose 1,5-bisphosphate carboxylase/​oxygenase (Rubisco) in chloroplasts...
April 22, 2017: Journal of Plant Research
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