Read by QxMD icon Read


Mitsunobu Takeda, Jun Koseki, Hidekazu Takahashi, Norikatsu Miyoshi, Naohiro Nishida, Junichi Nishimura, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Hirofumi Yamamoto, Hideshi Ishii, Yuichiro Doki, Masaki Mori, Naotsugu Haraguchi
Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSC remains a promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSC and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an anti-malarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug...
February 14, 2019: Cancer Research
Qiao Ye, Chaonan Zhang, Zhenlu Wang, Yongyong Feng, Aiguo Zhou, Shaolin Xie, Qiong Xiang, Enfeng Song, Jixing Zou
Koumine is a component of the Chinese medicinal herb Gelsemium elegans and is toxic to vertebrates. We used the ciliate Tetrahymena thermophila as a model to evaluate the toxic effects of this indole alkaloid in eukaryotic microorganisms. Koumine inhibited T. thermophila growth and viability in a dose-dependent manner. Moreover, this drug produced oxidative stress in T. thermophila cells and expressions of antioxidant enzymes were significantly elevated at high koumine levels (p < 0.05). Koumine also caused significant levels of apoptosis (p < 0...
2019: PloS One
Ning-Ping Zhang, Xue-Jing Liu, Li Xie, Xi-Zhong Shen, Jian Wu
Activation of inflammation is an important mechanism in the development of nonalcoholic steatohepatitis (NASH). This study aims to delineate how mitophagy affects NLRP3 inflammasome activation in hepatic lipotoxicity. Mice were fed a high fat/calorie diet (HFCD) for 24 weeks. Primary rat hepatocytes were treated with palmitic acid (PA) for various periods of time. Mitophagy was measured by protein levels of LC3II and P62. NLRP3, caspase-1, interleukin (IL)-18, and IL-1β at mRNA and protein levels were used as indicators of inflammasome activation...
January 30, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
Ulfuara Shefa, Na Young Jeong, In Ok Song, Hyung-Joo Chung, Dokyoung Kim, Junyang Jung, Youngbuhm Huh
Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases. Proper regulation of mitophagy is crucial for maintaining homeostasis; conversely, inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species, including reactive oxygen species and reactive nitrogen species, resulting in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis...
May 2019: Neural Regeneration Research
Hyo Won Chang, Mi Ra Kim, Hyang Ju Lee, Hye Min Lee, Gui Chul Kim, Yoon Sun Lee, Hae Yun Nam, Myungjin Lee, Hye Jin Jang, Kyung Eun Lee, Jong Cheol Lee, Youngro Byun, Seong Who Kim, Sang Yoon Kim
The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradiation showed decreased oxygen consumption and increased glycolysis with compromised mitochondria, corresponding with their enhanced sensitivity to drugs that target glycolysis. In contrast, radioresistant cancer cells with wild-type p53 preserved their primary metabolic profile with intact mitophagic processes and maintained their mitochondrial integrity...
January 21, 2019: Oncogene
Yea Seul Shin, James G Ryall, Joanne M Britto, Chew L Lau, Rodney J Devenish, Phillip Nagley, Philip M Beart
Contributions of damaged mitochondria to neuropathologies have stimulated interest in mitophagy. We investigated triggers of neuronal mitophagy by disruption of mitochondrial energy metabolism in primary neurons. Mitophagy was examined in cultured murine cerebellar granule cells after inhibition of mitochondrial respiratory chain by drugs rotenone, 3-nitropropionic acid, antimycin A and potassium cyanide, targeting complexes I, II, III and IV, respectively. Inhibitor concentrations producing slow cellular demise were determined from analyses of cellular viability, morphology of neuritic damage, plasma membrane permeability and oxidative phosphorylation...
January 21, 2019: Journal of Neurochemistry
Dominic D Quintana, Jorge A Garcia, Saumyendra N Sarkar, Sujung Jun, Elizabeth B Engler-Chiurazzi, Ashley E Russell, John Z Cavendish, James W Simpkins
Astrocytes serve to maintain proper neuronal function and support neuronal viability, but remain largely understudied in research of cerebral ischemia. Astrocytic mitochondria are core participants in the metabolic activity of astrocytes. The objective of this study is to assess astrocyte mitochondrial competence during hypoxia and post-hypoxia reoxygenation and to determine cellular adaptive and pathological changes in the mitochondrial network. We hypothesize that during metabolic distress in astrocytes; mitochondrial networks undergo a shift in fission-fusion dynamics that results in a change in the morphometric state of the entire mitochondrial network...
December 27, 2018: Mitochondrion
Seon Beom Song, Eun Seong Hwang
Glucose withdrawal has been used as a model for the study of homeostatic defense mechanisms, especially for how cells cope with a shortage of nutrient supply by enhancing catabolism. However, detailed cellular responses to glucose withdrawal have been poorly studied, and are controversial. In this study, we determined how glucose withdrawal affects mitochondrial activity, and the quantity and the role of SIRT1 in these changes. The results of our study indicate a substantial increase in ATP production from mitochondria, through an elevation of mitochondrial biogenesis, mediated by SIRT1 activation that is driven by increased NAD⁺/NADH ratio...
December 27, 2018: Cells
Qiao Ye, Yongyong Feng, Zhenlu Wang, Wenzhao Jiang, Yuexin Qu, Chaonan Zhang, Aiguo Zhou, Shaolin Xie, Jixing Zou
Gelsemine is an important toxic substance extracted from Gelsemium elegans , which has a lot of biological functions in cells and organisms, but its toxicity has been rarely reported in Tetrahymena thermophila . In this study, we used the protozoan T. thermophila as an experimental model to investigate the potential toxicity-induced mechanism of gelsemine in the unicellular eukaryote. Our results clearly showed gelsemine inhibited T. thermophila growth in a dose-dependent manner. This exposure also resulted in oxidative stress on T...
2018: PeerJ
Hyo Min Cho, Jae Ryun Ryu, Youhwa Jo, Tae Woong Seo, Ye Na Choi, June Hoan Kim, Jee Min Chung, Bongki Cho, Ho Chul Kang, Seong-Woon Yu, Soon Ji Yoo, Hyun Kim, Woong Sun
Mitophagy, a mitochondrial quality control process for eliminating dysfunctional mitochondria, can be induced by a response of dynamin-related protein 1 (Drp1) to a reduction in mitochondrial membrane potential (MMP) and mitochondrial division. However, the coordination between MMP and mitochondrial division for selecting the damaged portion of the mitochondrial network is less understood. Here, we found that MMP is reduced focally at a fission site by the Drp1 recruitment, which is initiated by the interaction of Drp1 with mitochondrial zinc transporter Zip1 and Zn2+ entry through the Zip1-MCU complex...
December 1, 2018: Molecular Cell
Giselli Scaini, Tatiana Barichello, Gabriel R Fries, Elizabeth A Kennon, Taylor Andrews, Bobby R Nix, Giovana Zunta-Soares, Samira S Valvassori, Jair C Soares, João Quevedo
Bipolar disorder (BD) is a chronic, debilitating illness with a global prevalence of up to 4.8%. The importance of understanding how dysfunctional mitochondria and mitophagy contribute to cell survival and death in BD is becoming increasingly apparent. Therefore, the purpose of this study was to evaluate the mitophagic pathway and NLRP3 inflammasome activation in peripheral blood mononuclear cells (PBMCs) of patients with BD and healthy individuals. Since 18-kDa translocator protein (TSPO) plays an important role in regulating mitochondrial function and since TSPO itself impairs cellular mitophagy, we also investigated the changes in the TSPO-related pathway...
December 11, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Eugene P Sokolov, Stephanie Markert, Tjorven Hinzke, Claudia Hirschfeld, Dörte Becher, Siriluck Ponsuksili, Inna M Sokolova
Mitochondria are key intracellular targets of hypoxia-reoxygenation (H/R) stress due to their central role in generation of ATP and reactive oxygen species (ROS). Intertidal oysters Crassostrea gigas are adapted to frequent H/R cycles and maintain aerobic function despite frequent oxygen fluctuations. To gain insight into the molecular mechanisms of H/R tolerance, we assessed changes in mitochondrial respiration and (phospho)proteome of C. gigas during hypoxia and recovery. Oyster mitochondria maintained OXPHOS capacity despite a decline in cytochrome c oxidase activity during H/R stress...
December 11, 2018: Journal of Proteomics
Christian Galasso, Genoveffa Nuzzo, Christophe Brunet, Adrianna Ianora, Angela Sardo, Angelo Fontana, Clementina Sansone
Marine dinoflagellates are a valuable source of bioactive molecules. Many species produce cytotoxic compounds and some of these compounds have also been investigated for their anticancer potential. Here, we report the first investigation of the toxic dinoflagellate Alexandrium minutum as source of water-soluble compounds with antiproliferative activity against human lung cancer cells. A multi-step enrichment of the phenol⁻water extract yielded a bioactive fraction with specific antiproliferative effect (IC50 = 0...
December 12, 2018: Marine Drugs
Åsa B Gustafsson, Gerald W Dorn
The central functions fulfilled by mitochondria as both energy generators essential for tissue homeostasis and gateways to programmed apoptotic and necrotic cell death mandate tight control over the quality and quantity of these ubiquitous endosymbiotic organelles. Mitophagy, the targeted engulfment and destruction of mitochondria by the cellular autophagy apparatus, has conventionally been considered as the mechanism primarily responsible for mitochondrial quality control. However, our understanding of how, why, and under what specific conditions mitophagy is activated has grown tremendously over the past decade...
January 1, 2019: Physiological Reviews
Prakash P Praharaj, Prajna P Naik, Debasna P Panigrahi, Chandra S Bhol, Kewal K Mahapatra, Srimanta Patra, Gautam Sethi, Sujit Kumar Bhutia
The efficacy of chemotherapy is mostly restricted by the drug resistance developed during the course of cancer treatment. Mitophagy, as a pro-survival mechanism, crucially maintains mitochondrial homeostasis and it is one of the mechanisms that cancer cells adopt for their progression. On the other hand, mitochondrial apoptosis, a precisely regulated form of cell death, acts as a tumor-suppressive mechanism by targeting cancer cells. Mitochondrial lipids, such as cardiolipin, ceramide, and sphingosine-1-phosphate, act as a mitophageal signal for the clearance of damaged mitochondria by interacting with mitophagic machinery as well as activate mitochondrial apoptosis via the release of cytochrome c into the cytoplasm...
December 11, 2018: Cellular and Molecular Life Sciences: CMLS
Dzhamilja Safiulina, Malle Kuum, Vinay Choubey, Nana Gogichaishvili, Joanna Liiv, Miriam A Hickey, Michal Cagalinec, Merle Mandel, Akbar Zeb, Mailis Liiv, Allen Kaasik
The Parkinson's disease-associated protein kinase PINK1 and ubiquitin ligase Parkin coordinate the ubiquitination of mitochondrial proteins, which marks mitochondria for degradation. Miro1, an atypical GTPase involved in mitochondrial trafficking, is one of the substrates tagged by Parkin after mitochondrial damage. Here, we demonstrate that a small pool of Parkin interacts with Miro1 before mitochondrial damage occurs. This interaction does not require PINK1, does not involve ubiquitination of Miro1 and also does not disturb Miro1 function...
November 30, 2018: EMBO Journal
Diego Grassi, Natalia Diaz-Perez, Laura A Volpicelli-Daley, Corinne Ida Lasmézas
We recently identified a truncated and phosphorylated form of α-synuclein, pα-syn*, as a key neurotoxic α-synuclein species found in cultured neurons, as well as in mouse and Parkinson's disease patients' brains. Small pα-syn* aggregates localize to mitochondria and induce mitochondrial damage and fragmentation. Herein, we investigated the molecular basis of pα-syn*-induced toxicity. By immunofluorescence, we found phosphorylated MKK4, JNK, ERK5 and p38 MAPKs in pα-syn* inclusions. pJNK colocalized with pα-syn* at mitochondria and mitochondria-associated ER membranes where it was associated with BiP and pACC1, markers for the ER and energy deprivation, respectively...
November 22, 2018: Neurobiology of Disease
Lu He, Qionglin Zhou, Zheng Huang, Jin Xu, Hong Zhou, Deguan Lv, Liqun Lu, Shifang Huang, Mingzhu Tang, Jiuchang Zhong, Jianxiong Chen, Xulin Luo, Lanfang Li, Linxi Chen
Aberrant proliferation of vascular smooth muscle cells (VSMC) is a critical contributor to the pathogenesis of atherosclerosis (AS). Our previous studies have demonstrated that apelin-13/APJ confers a proliferative response in VSMC, however, its underlying mechanism remains elusive. In this study, we aimed to investigate the role of mitophagy in apelin-13-induced VSMC proliferation and atherosclerotic lesions in apolipoprotein E knockout (ApoE-/-) mice. Apelin-13 enhances human aortic VSMC proliferation and proliferative regulator proliferating cell nuclear antigen expression in dose and time-dependent manner, while is abolished by APJ antagonist F13A...
November 19, 2018: Journal of Cellular Physiology
Ilaria Bellezza
Age-related macular degeneration is one of the leading causes of vision loss in the elderly. Genetics, environmental insults, and age-related issues are risk factors for the development of the disease. All these risk factors are linked to the induction of oxidative stress. In young subjects retinal pigment epithelial cells mitigate reactive oxygen generation by the elimination of dysfunctional mitochondria, via mitophagy, and by increasing antioxidant defenses via Nrf2 activation. The high amount of UV light absorbed by the retina, together with cigarette smoking, cooperate with the aging process to increase the amount of reactive oxygen species generated by retinal pigment epithelium where oxidative stress arises...
2018: Frontiers in Pharmacology
Roberta Coluccia, Salvatore Raffa, Danilo Ranieri, Andrea Micaloni, Sabatino Valente, Gerardo Salerno, Cristina Scrofani, Marco Testa, Giovanna Gallo, Erika Pagannone, Maria Rosaria Torrisi, Massimo Volpe, Speranza Rubattu
Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects...
October 12, 2018: Oncotarget
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"