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Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K Jaiswal, Anamaris M Colberg-Poley
Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM...
December 2017: Scientific Reports
Fan Yang, Xiangjing Yu, Ting Li, Jianjun Wu, YaJun Zhao, Jiaqi Liu, Aili Sun, Shiyun Dong, Jichao Wu, Xin Zhong, Changqing Xu, Fanghao Lu, Weihua Zhang
BACKGROUND: The upregulation of reactive oxygen species (ROS) is a primary cause of cardiomyocyte apoptosis in Diabetes cardiomyopathy (DCM). Mitofusin-2 (Mfn-2) is a key protein that bridges the mitochondria and endoplasmic reticulum(ER). Hydrogen sulfide (H2S)-mediated cardioprotection is related to antioxidant effects. The present study demonstrated that H2S inhibited the interaction between the ER and mitochondrial apoptotic pathway. METHODS: This study investigated cardiac function, ultrastructural changes in the ER and mitochondria, apoptotic rate using TUNEL and the expression of ER stress-associated proteins and mitochondrial apoptotic proteins in cardiac tissues in STZ-induced type I diabetic rats treated with or without NaHS (donor of H2S)...
December 20, 2016: American Journal of Physiology. Endocrinology and Metabolism
Yuanbo Qi, Liming Yan, Caiting Yu, Xiangyang Guo, Xin Zhou, Xiaoyu Hu, Xiaofang Huang, Zihe Rao, Zhiyong Lou, Junjie Hu
Mitochondria undergo fusion and fission. The merging of outer mitochondrial membranes requires mitofusin (MFN), a dynamin-like GTPase. How exactly MFN mediates membrane fusion is poorly understood. Here, we determined crystal structures of a minimal GTPase domain (MGD) of human MFN1, including the predicted GTPase and the distal part of the C-terminal tail (CT). The structures revealed that a helix bundle (HB) formed by three helices extending from the GTPase and one extending from the CT closely attaches to the GTPase domain, resembling the configuration of bacterial dynamin-like protein...
December 5, 2016: Journal of Cell Biology
Wei Peng, Wei Lan, Zeng Yu, Jianxin Wang, Yi Pan
MicroRNAs have close relationship with human diseases. Therefore, identifying disease related MicroRNAs plays an important role in disease diagnosis, prognosis and therapy. However, designing an effective computational method which can make good use of various biological resources and correctly predict the associations between MicroRNA and disease is still a big challenge. Previous researchers have pointed out that there are complex relationships among microRNAs, diseases and environment factors. There are inter-relationships between microRNAs, diseases or environment factors based on their functional similarity or phenotype similarity or chemical structure similarity and so on...
November 29, 2016: IEEE Transactions on Nanobioscience
Luke E Formosa, Michael T Ryan
In this issue, Qi et al. (2016. J. Cell Biol provide structural insights into the mechanisms of mitochondrial outer membrane fusion by investigating the structure of mitofusin 1 (MFN1). This work proposes a new model to explain the important and elusive process of MFN-mediated mitochondrial fusion.
December 5, 2016: Journal of Cell Biology
Omar Emiliano Aparicio-Trejo, Edilia Tapia, Eduardo Molina-Jijón, Omar Noel Medina-Campos, Norma Angélica Macías-Ruvalcaba, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Fernando E García-Arroyo, Magdalena Cristóbal, Laura Gabriela Sánchez-Lozada, José Pedraza-Chaverri
Five-sixths nephrectomy (5/6NX) is a widely used model to study the mechanisms leading to renal damage in chronic kidney disease (CKD). However, early alterations on renal function, mitochondrial dynamics, and oxidative stress have not been explored yet. Curcumin is an antioxidant that has shown nephroprotection in 5/6NX-induced renal damage. The aim of this study was to explore the effect of curcumin on early mitochondrial alterations induced by 5/6NX in rats. In isolated mitochondria, 5/6NX-induced hydrogen peroxide production was associated with decreased activity of complexes I and V, decreased activity of antioxidant enzymes, alterations in oxygen consumption and increased MDA-protein adducts...
November 1, 2016: BioFactors
Antonietta Franco, Richard N Kitsis, Julie A Fleischer, Evripidis Gavathiotis, Opher S Kornfeld, Guohua Gong, Nikolaos Biris, Ann Benz, Nir Qvit, Sara K Donnelly, Yun Chen, Steven Mennerick, Louis Hodgson, Daria Mochly-Rosen, Gerald W Dorn
Mitochondria are dynamic organelles that exchange contents and undergo remodelling during cyclic fusion and fission. Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A). It has not yet been possible to directly modulate mitochondrial fusion, in part because the structural basis of mitofusin function is not completely understood. Here we show that mitofusins adopt either a fusion-constrained or a fusion-permissive molecular conformation, directed by specific intramolecular binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulated in mouse cells by targeting these conformational transitions...
December 1, 2016: Nature
Yanlong Qu, Li Zhou, Chunlei Wang
Inflammation has been reported to play critical roles in the development of osteoarthritis. In the present study, we investigated whether mangiferin (MFN) had anti-inflammatory effects in IL-1β-stimulated human osteoarthritis chondrocytes. The cells were treated with various concentrations of MFN in the presence or absence of IL-1β. The production of MMP-1, MMP-3, PGE2, and NO was measured in this study. The expression of NF-kB and PPAR-γ was detected by western blot analysis. MFN inhibited IL-1β-induced inflammatory mediators PGE2 and NO production...
October 12, 2016: Inflammation
Deborah Naon, Marta Zaninello, Marta Giacomello, Tatiana Varanita, Francesca Grespi, Sowmya Lakshminaranayan, Annalisa Serafini, Martina Semenzato, Stephanie Herkenne, Maria Isabel Hernández-Alvarez, Antonio Zorzano, Diego De Stefani, Gerald W Dorn, Luca Scorrano
The discovery of the multiple roles of mitochondria-endoplasmic reticulum (ER) juxtaposition in cell biology often relied upon the exploitation of Mitofusin (Mfn) 2 as an ER-mitochondria tether. However, this established Mfn2 function was recently questioned, calling for a critical re-evaluation of Mfn2's role in ER-mitochondria cross-talk. Electron microscopy and fluorescence-based probes of organelle proximity confirmed that ER-mitochondria juxtaposition was reduced by constitutive or acute Mfn2 deletion...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Wenwen Li, Tao Sun, Beibei Liu, Di Wu, Wenfeng Qi, Xianhua Wang, Qi Ma, Heping Cheng
Mitochondria are highly dynamic organelles undergoing constant network reorganization and exhibiting stochastic signaling events in the form of mitochondrial flashes (mitoflashes). Here we investigate whether and how mitochondrial network dynamics regulate mitoflash biogenesis and signaling. We found that mitoflash frequency was largely invariant when network fragmentized or redistributed in the absence of mitofusin (Mfn) 1, Mfn2, or Kif5b. However, Opa1 deficiency decreased spontaneous mitoflash frequency due to superimposing changes in respiratory function, whereas mitoflash response to non-metabolic stimulation was unchanged despite network fragmentation...
2016: Scientific Reports
Xiao-Wen Liu, Ping Yuan, Jun Tian, Ling-Jun Li, Yu Wang, Song-Chun Huang, Lin Liu, Claude Backendorf, Mathieu H M Noteborn, Jun Sun
Worldwide, cervix carcinoma is among the most dangerous cancer types, and novel therapies are under development. Cancer treatments are often hampered because of lack of specificity. The chicken anemia virus-derived apoptin induces apoptosis selectively in tumor cells and leaves normal cells unharmed. Here, we have carried out in-vitro and in-vivo studies on the cytotoxic effect of apoptin in a cervix carcinoma model. Apoptin was fused to the protein transduction domain 4 (PTD4), enabling delivery of the fusion protein across cellular membranes...
November 2016: Anti-cancer Drugs
Da-Jian Zhu, Yan-Feng Huang, Xiao-Wu Chen, Zhen-Tao Luo, Guo-Xin Wang, Chang-Chun Liu, Wei-Jie Zhang, Man-Zhao Ouyang
OBJECTIVE: Development of treatment resistance and adverse toxicity limits the gains made by irinotecan in patients with colorectal cancer. According to our previous studies, we found that curcumin could enhance the efficacy of irinotecan-induced apoptosis of colorectal tumor cells in vitro. This study aims to examine the effectiveness of a combination treatment regimen of irinotecan and curcumin in the colorectal cancer xenograft model. RESULTS: Curcumin or irinotecan alone reduced the tumor volume, and the combination had the strongest anticancer effects...
July 14, 2016: Oncotarget
Thaline de Quadros, Heloísa Schramm, Eliane C Zeni, Carmen Simioni, Silvana Allodi, Yara M R Müller, Dib Ammar, Evelise M Nazari
In South America, increased UVB radiation has become an important environmental issue that is potentially threatening aquatic ecosystems. Considering that species exhibit different degrees of sensitivity to UVB radiation and that embryos are more sensitive than organisms at later life stages, the aim of this study was to characterize the effects of UVB radiation on subcellular compartments of embryos of the freshwater prawn Macrobrachium olfersi. This species lives and reproduces in clear and shallow waters, where UV radiation can fully penetrates...
October 2016: Ecotoxicology and Environmental Safety
Stefon J R Van Noordt, Allan Campopiano, Sidney J Segalowitz
Theta oscillations in the EEG have been linked to several ERPs that are elicited during performance-monitoring tasks, including the error-related negativity (ERN), no-go N2, and the feedback-related negativity (FRN). We used a novel paradigm to isolate independent components (ICs) in single subjects' (n = 27) EEG accounting for a medial frontal negativity (MFN) to response cue stimuli that signal a potential change in future response demands. Medial frontal projecting ICs that were sensitive to these response cues also described the ERNs, no-go N2s, and, to a lesser extent, the FRNs, that were elicited in letter flanker, go/no-go, and time-estimation tasks, respectively...
September 2016: Psychophysiology
Swati Agarwal, Anuradha Yadav, Shashi Kant Tiwari, Brashket Seth, Lalit Kumar Singh Chauhan, Puneet Khare, Ratan Singh Ray, Rajnish Kumar Chaturvedi
The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs)...
July 29, 2016: Journal of Biological Chemistry
Gabriel Gaudencio Rêgo, Camila Campanhã, Julia Horta Tabosa do Egito, Paulo Sérgio Boggio
The Ultimatum Game (UG) is an endowment sharing game in which a proposer suggests a division of an asset to a recipient, who must accept or reject it. Economic studies showed that despite recipients usually reject unfair offers, perception and reaction to unfairness is highly dependent on who is the proposer. Event related potentials (ERP) commonly detected in UG games are the Medial Frontal Negativity (MFN), a component detected in recipients facing unfair offers, and the P300, a component related to attentional and memory processes...
May 30, 2016: Social Neuroscience
Ji-Wook Kim, Jae-Hyun Lee, Ji-Hyun Ma, Eunna Chung, Hongsuh Choi, Jinwoong Bok, Jinwoo Cheon
Sound perception via mechano-sensation is a remarkably sensitive and fast transmission process, converting sound as a mechanical input to neural signals in a living organism. Although knowledge of auditory hair cell functions has advanced over the past decades, challenges remain in understanding their biomechanics, partly because of their biophysical complexity and the lack of appropriate probing tools. Most current studies of hair cells have been conducted in a relatively low-frequency range (<1000 Hz); therefore, fast kinetic study of hair cells has been difficult, even though mammalians have sound perception of 20 kHz or higher...
June 8, 2016: Nano Letters
Emanuele Marzetti, Riccardo Calvani, Maria Lorenzi, Fabiana Tanganelli, Anna Picca, Maurizio Bossola, Amerigo Menghi, Roberto Bernabei, Francesco Landi
BACKGROUND: Sarcopenia has been proposed as a potentially amenable factor impacting the clinical outcomes of hip-fractured elderly. The identification of specific biological targets is therefore crucial to developing pharmacological interventions against age-related muscle wasting. The present work reports promising preliminary data on the association between alterations of myocyte quality control (MQC) signaling and sarcopenia in old patients with hip fracture. METHODS: Twenty-five elderly hip-fractured patients (20 women and 5 men; mean age 84...
July 2016: Experimental Gerontology
Sérgio Luiz Gama Nogueira-Filho, Ivanise da Hora Bastos, Alcester Mendes, Selene Siqueira da Cunha Nogueira
We conducted a nitrogen balance digestion trial to determine the crude protein requirements of paca (Cuniculus paca) during the last growth phase. In a 4 × 4 Latin square design, four young captive male pacas, aged 5 months, were fed four isoenergetic diets containing four different levels of nitrogen (N) (11.3, 16.6, 21.4, and 26.6 g N/kg of dry matter). After 15 days of adaptation, we collected all feces and urine for five consecutive days. By regression analysis between N intake and N in feces and urine, the metabolic fecal nitrogen (MFN = 4...
June 2016: Tropical Animal Health and Production
Guangrong Wang, Jianbiao Li, Zheng Li, Mengxing Wei, Shaodong Li
Inequality aversion is a typical form of fairness preferences, which can explain the behaviors in many social exchange situations such as the ultimatum game (UG). There are two kinds of inequality aversion-disadvantageous inequality aversion of responders and advantageous inequality aversion of proposers in the ultimatum game. Although neuroscience research has reported neural correlates of disadvantageous inequality aversion, there are still debates about advantageous inequality aversion of proposers. In this paper, we developed a variant of ultimatum game in which participants played the UG as proposers...
May 15, 2016: Brain Research
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