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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/28448247/oleuropein-isolated-from-fraxinus-rhynchophylla-inhibits-glutamate-induced-neuronal-cell-death-by-attenuating-mitochondrial-dysfunction
#2
Mi Hye Kim, Ju-Sik Min, Joon Yeop Lee, Unbin Chae, Eun-Ju Yang, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells...
April 27, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28436948/mitochondrial-elongation-mediated-glucose-metabolism-reprogramming-is-essential-for-tumour-cell-survival-during-energy-stress
#3
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/28435473/downregulation-of-mitochondrial-cyclooxygenase-2-inhibits-the-stemness-of-nasopharyngeal-carcinoma-by-decreasing-the-activity-of-dynamin-related-protein-1
#4
Teng-Jian Zhou, Shi-Li Zhang, Cheng-Yong He, Qun-Ying Zhuang, Pei-Yu Han, Sheng-Wei Jiang, Huan Yao, Yi-Jun Huang, Wen-Hua Ling, Yu-Chun Lin, Zhong-Ning Lin
Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues...
2017: Theranostics
https://www.readbyqxmd.com/read/28432138/inhibition-of-drp1-ameliorates-synaptic-depression-a%C3%AE-deposition-and-cognitive-impairment-in-alzheimer-s-disease-model
#5
Seung-Hyun Baek, So Jung Park, Jae In Jeong, Sung Hyun Kim, Jihoon Han, Jae Won Kyung, Sang-Ha Baik, Yuri Choi, Bo-Youn Choi, Jinsu Park, Gahee Bahn, Ji Hyun Shin, Doo Sin Jo, Joo-Yong Lee, Choon-Gon Jang, Thiruma V Arumugam, Jongpil Kim, Jeung-Whan Han, Jae-Young Koh, Dong-Hyung Cho, Dong-Gyu Jo
Excessive mitochondrial fission is a prominent early event, and contributes to mitochondrial dysfunction, synaptic failure and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examine the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric β-amyloid (Aβ) in neurons, and neuropathology and cognitive functions in APP/PS1 double transgenic AD mice...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28423551/metabolic-reprogramming-of-the-premalignant-colonic-mucosa-is-an-early-event-in-carcinogenesis
#6
Mart Dela Cruz, Sarah Ledbetter, Sanjib Chowdhury, Ashish K Tiwari, Navneet Momi, Ramesh K Wali, Charles Bliss, Christopher Huang, David Lichtenstein, Swati Bhattacharya, Anisha Varma-Wilson, Vadim Backman, Hemant K Roy
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423497/drp1-dependent-mitophagy-protects-against-cisplatin-induced-apoptosis-of-renal-tubular-epithelial-cells-by-improving-mitochondrial-function
#7
Chuanyan Zhao, Zhuyun Chen, Jia Qi, Suyan Duan, Zhimin Huang, Chengning Zhang, Lin Wu, Ming Zeng, Bo Zhang, Ningning Wang, Huijuan Mao, Aihua Zhang, Changying Xing, Yanggang Yuan
Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients. There is increasing evidence that mitochondrial dysfunction plays an important role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is carried out by mitophagy. Although mitophagy is considered of particular importance in protecting against AKI, little is known of the precise role of mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity. Also, evidence that activation of mitophagy improved mitochondrial function is lacking...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414272/regulation-of-mitochondria-dynactin-interaction-and-mitochondrial-retrograde-transport-in-axons
#8
Catherine M Drerup, Amy L Herbert, Kelly R Monk, Alex V Nechiporuk
Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes...
April 17, 2017: ELife
https://www.readbyqxmd.com/read/28411026/drp1-mediates-compression-induced-programmed-necrosis-of-rat-nucleus-pulposus-cells-by-promoting-mitochondrial-translocation-of-p53-and-nuclear-translocation-of-aif
#9
Hui Lin, Lei Zhao, Xuan Ma, Bai-Chuan Wang, Xiang-Yu Deng, Min Cui, Song-Feng Chen, Zeng-Wu Shao
Compression-induced programmed cell death of nucleus pulposus (NP) cells is an important contributor to intervertebral disc degeneration (IDD). Dynamin-related protein 1 (Drp1), a crucial mitochondrial fission protein, triggers programmed necrosis upon cellular injury. However, limited information is available about the role of Drp1 in compression-induced programmed necrosis of NP cells. In the present study, we found that compression resulted in upregulation and mitochondrial translocation of Drp1. Inhibition of Drp1 by siRNA or mitochondrial division inhibitor 1 (mdivi-1) effectively prevented the programmed necrosis of NP cells treated with compression...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28410195/antagonistic-effects-of-selenium-on-lead-induced-autophagy-by-influencing-mitochondrial-dynamics-in-the-spleen-of-chickens
#10
Yujing Han, Chunqiu Li, Mingjun Su, Zhihui Wang, Ning Jiang, Dongbo Sun
Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has antagonistic effects on Pb. In our study, brown layer chickens were randomly allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and 350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the 90th day; spleen tissues were subjected to observation of ultrastructure and detection of spleen-related indexes. The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin (mTOR) was downregulated...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409745/mitochondria-division-inhibitor-1-protects-against-amyloid-%C3%AE-induced-mitochondrial-fragmentation-and-synaptic-damage-in-alzheimer-s-disease
#11
P Hemachandra Reddy, Maria Manczak, XiangLing Yin
The purpose our study was to determine the protective effects of mitochondria division inhibitor 1 (Mdivi1) in Alzheimer's disease (AD). Mdivi1 is hypothesized to reduce excessive fragmentation of mitochondria and mitochondrial dysfunction in AD neurons. Very little is known about whether Mdivi1 can confer protective effects in AD. In the present study, we sought to determine the protective effects of Mdivi1 against amyloid-β (Aβ)- and mitochondrial fission protein, dynamin-related protein 1 (Drp1)-induced excessive fragmentation of mitochondria in AD progression...
April 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28409163/pgc1%C3%AE-activators-mitigate-diabetic-tubulopathy-by-improving-mitochondrial-dynamics-and-quality-control
#12
So-Young Lee, Jun Mo Kang, Dong-Jin Kim, Seon Hwa Park, Hye Yun Jeong, Yu Ho Lee, Yang Gyun Kim, Dong Ho Yang, Sang Ho Lee
Purpose. In this study, we investigated the effect of PGC1α activators on mitochondrial fusion, fission, and autophagic quality control in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether the upregulation of PGC1α attenuates diabetic tubulopathy by normalizing mitochondrial homeostasis. Methods. HKC8 cells were subjected to high-glucose conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28408823/gold-nanoparticles-enhance-trail-sensitivity-through-drp1-mediated-apoptotic-and-autophagic-mitochondrial-fission-in-nsclc-cells
#13
Sunkui Ke, Tong Zhou, Peiyan Yang, Yange Wang, Peng Zhang, Keman Chen, Lei Ren, Shefang Ye
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its agonistic receptors have been identified as highly promising antitumor agents preferentially eliminating cancer cells with minimal damage, the emergence of TRAIL resistance in most cancers may contribute to therapeutic failure. Thus, there is an urgent need for new approaches to overcome TRAIL resistance. Gold nanoparticles (AuNPs) are one of the most promising nanomaterials that show immense antitumor potential via targeting various cellular and molecular processes; however, the effects of AuNPs on TRAIL sensitivity in cancer cells remain unclear...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28408736/mief1-2-function-as-adaptors-to-recruit-drp1-to-mitochondria-and-regulate-the-association-of-drp1-with-mff
#14
Rong Yu, Tong Liu, Shao-Bo Jin, Chenfei Ning, Urban Lendahl, Monica Nistér, Jian Zhao
Mitochondrial dynamics is a fundamental cellular process and recruitment of Drp1 to mitochondria is an essential step in mitochondrial fission. Mff and MIEF1/2 (MiD51/49) serve as key receptors for recruitment of Drp1 to mitochondria in mammals. However, if and how these receptors work together in mitochondrial fission is poorly understood. Here we show that MIEFs interact with both Drp1 and Mff on the mitochondrial surface and serve as adaptors linking Drp1 and Mff together in a trimeric Drp1-MIEF-Mff complex...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28398674/melatonin-protects-cardiac-microvasculature-against-ischemia-reperfusion-injury-via-suppression-of-mitochondrial-fission-vdac1-hk2-mptp-mitophagy-axis
#15
Hao Zhou, Ying Zhang, Shunying Hu, Chen Shi, Pingjun Zhu, Qiang Ma, Qinhua Jin, Feng Cao, Feng Tian, Yundai Chen
The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow and lower microcirculation perfusion defects...
April 11, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28388678/drp1-dependent-mitochondrial-fission-mediates-osteogenic-dysfunction-in-inflammation-through-elevated-production-of-reactive-oxygen-species
#16
Ling Zhang, Xueqi Gan, Yuting He, Zhuoli Zhu, Junfei Zhu, Haiyang Yu
Although previous studies have implicated pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), to be detrimental for osteogenic activity, the related regulatory mechanisms are not yet fully validated. Since mitochondria host several essential metabolic processes and play a pivotal role in cellular functions, whether and how mitochondrial function contributes to inflammation-induced bone destruction needs further exploration. Our findings revealed that TNF-α impaired osteoblast function, including decreased mRNA levels of osteogenic markers, suppressed ALP expression and activity, and compromised cellular viability...
2017: PloS One
https://www.readbyqxmd.com/read/28385187/anti-inflammatory-effect-of-oleuropein-on-microglia-through-regulation-of-drp1-dependent-mitochondrial-fission
#17
Junghyung Park, Ju-Sik Min, Unbin Chae, Joon Yeop Lee, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Oleuropein is a primary phenolic compound found in olive leaf and Fraxinus rhynchophylla. Here, we investigated the impact of oleuropein on LPS-induced BV-2 microglial cells. Oleuropein suppressed the LPS-induced increase in pro-inflammatory mediators, such as nitric oxide, and pro-inflammatory cytokines, via inhibition of ERK/p38/NF-κB activation and reactive oxygen species (ROS) generation. Furthermore, it suppressed LPS-induced excessive mitochondrial fission, which regulates mitochondrial ROS generation and pro-inflammatory response by diminishing Drp1 dephosphorylation...
May 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28383775/polydatin-impairs-mitochondria-fitness-and-ameliorates-podocyte-injury-by-suppressing-drp1-expression
#18
Ni Zheng, Tao Liang, Xiaohui Xu, Zelin Zhao, Jiangang Liu, Zhao Song, Weikang Huo, Hongchao Xu, Qiujing Wang, Xin Li
Polydatin (PD), a resveratrol glycoside, has been shown to protect renal function in diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. This study demonstrates that PD stabilize the mitochondrial morphology and attenuate mitochondrial malfunction in both KKAy mice and in hyperglycemia (HG)-induced MPC5 cells. We use western blot analysis to demonstrate that PD reversed podocyte apoptosis induced by HG via suppressing dynamin-related protein 1 (Drp1). This effect may depend on the ability of PD to inhibit the generation of cellular reactive oxygen species (ROS)...
April 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28379197/abnormalities-of-mitochondrial-dynamics-in-neurodegenerative-diseases
#19
REVIEW
Ju Gao, Luwen Wang, Jingyi Liu, Fei Xie, Bo Su, Xinglong Wang
Neurodegenerative diseases are incurable and devastating neurological disorders characterized by the progressive loss of the structure and function of neurons in the central nervous system or peripheral nervous system. Mitochondria, organelles found in most eukaryotic cells, are essential for neuronal survival and are involved in a number of neuronal functions. Mitochondrial dysfunction has long been demonstrated as a common prominent early pathological feature of a variety of common neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD)...
April 5, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28363867/developmentally-regulated-gtp-binding-protein-2-depletion-leads-to-mitochondrial-dysfunction-through-downregulation-of-dynamin-related-protein-1
#20
Mai-Tram Vo, Myoung Seok Ko, Unn Hwa Lee, Eun Hye Yoon, Byung Ju Lee, Wha Ja Cho, Chang Man Ha, Kyungjin Kim, Jeong Woo Park
Mitochondrial dynamics, including constant fusion and fission, play critical roles in maintaining mitochondrial morphology and function. Here, we report that developmentally regulated GTP-binding protein 2 (DRG2) regulates mitochondrial morphology by modulating the expression of the mitochondrial fission gene dynamin-related protein 1 (Drp1). shRNA-mediated silencing of DRG2 induced mitochondrial swelling, whereas expression of an shRNA-resistant version of DRG2 decreased mitochondrial swelling in DRG2-depleted cells...
May 13, 2017: Biochemical and Biophysical Research Communications
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