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Oliver Edenharter, Stephan Schneuwly, Juan A Navarro
Friedreich's ataxia (FRDA) is the most important recessive ataxia in the Caucasian population. It is caused by a deficit of the mitochondrial protein frataxin. Despite its pivotal effect on biosynthesis of iron-sulfur clusters and mitochondrial energy production, little is known about the influence of frataxin depletion on homeostasis of the cellular mitochondrial network. We have carried out a forward genetic screen to analyze genetic interactions between genes controlling mitochondrial homeostasis and Drosophila frataxin...
2018: Frontiers in Molecular Neuroscience
Yinfang Wang, Yitong Huang, Youbin Liu, Jinping Li, Yilong Hao, Peihao Yin, Zongjun Liu, Jingzhou Chen, Ying Wang, Nanping Wang, Peng Zhang
Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knock down of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jinpeng Li, Megumi Kanasaki, Ling Xu, Munehiro Kitada, Kenji Nagao, Yusuke Adachi, Hiroko Jinzu, Yasushi Noguchi, Miyuki Kohno, Keizo Kanasaki, Daisuke Koya
Muscle biology is important topic in diabetes research. We have reported that a diet with ketogenic amino acids rich replacement (KAAR) ameliorated high-fat diet (HFD)-induced hepatosteatosis via activation of the autophagy system. Here, we found that a KAAR ameliorated the mitochondrial morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles. The mice were fed with a standard HFD (30% fat in food) or an HFD with KAAR (HFDKAAR )...
March 14, 2018: Biochimica et Biophysica Acta
Anna Pellattiero, Luca Scorrano
Despite the significance of mitochondrial dynamics in many diseases, drugs that modulate it are lacking. In this issue of Cell Chemical Biology, Miret-Casals et al. (2018) use a phenotypic high-throughput screen to discover a pro-fusion role for the anti-inflammatory drug Leflunomide, paving the way to screen for mitochondrial pro-fusion drug candidates.
March 15, 2018: Cell Chemical Biology
Zhen Bao, Weijun Chen, Fan Pan, Bo Peng, Jin Gong
The purpose of the present study was to investigate the effect of breviscapine injection on hepatic ischemia/reperfusion (I/R) injury in rats. To explore the relevance and discuss the underlying mechanism of mitofusin 2 (Mfn2) in hepatic I/R injury, 40 Sprague-Dawley male rats were randomly and equally divided into five groups (n=8 per group) as follows: Sham, I/R + normal saline 1 (NS1), I/R + breviscapine 1 (Bre1), I/R + NS2 and I/R + Bre2 groups. Groups 1 and 2 represented ischemia for 20 and 60 min, respectively...
April 2018: Experimental and Therapeutic Medicine
Keigo Tsushida, Katsuyuki Tanabe, Kana Masuda, Satoshi Tanimura, Hiromasa Miyake, Yuka Arata, Hitoshi Sugiyama, Jun Wada
Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin...
March 12, 2018: Biochemical and Biophysical Research Communications
Summer J Rozzi, Valeria Avdoshina, Jerel A Fields, Italo Mocchetti
Human immunodeficiency virus-1 (HIV) infection of the central nervous system promotes neuronal injury that culminates in HIV-associated neurocognitive disorders. Viral proteins, including transactivator of transcription (Tat), have emerged as leading candidates to explain HIV-mediated neurotoxicity, though the mechanisms remain unclear. Tat transgenic mice or neurons exposed to Tat, which show neuronal loss, exhibit smaller mitochondria as compared to controls. To provide an experimental clue as to which mechanisms are used by Tat to promote changes in mitochondrial morphology, rat cortical neurons were exposed to Tat (100 nM) for various time points...
December 2018: Cell Death Discovery
Pedro J Tomaselli, Mahima Kapoor, Andrea Cortese, James M Polke, Alexander M Rossor, Mary M Reilly
Mutations in mitofusin 2 (MFN2) are the most common cause of axonal Charcot Marie Tooth disease (CMT2) (Polke; 2011). Additional features known to occasionally occur with MFN2-related disorders are optic atrophy, pyramidal signs, scoliosis and deafness (Zuchner, 2006; Feely, 2011; Bombelli, 2014). Cognitive impairment has been reported in a small number of patients with MFN2 mutations (Del Bo, 2008; Genari, 2011; Tufano, 2015).
March 9, 2018: Journal of the Peripheral Nervous System: JPNS
Tianzheng Yu, Iman Ferdjallah, Falicia Elenberg, Star K Chen, Patricia Deuster, Yifan Chen
AIMS: We have previously demonstrated in vitro that heat-induced skeletal muscle damage is associated with an increase in dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and no change in mitochondrial fusion. In this study, we investigated the in vivo effects of mitochondrial fission inhibition on heat-induced oxidative skeletal muscle injury and hyperthermic response in mice. MAIN METHODS: Core body temperatures of mice pre-treated with vehicle or Mdivi-1 were recorded by radio telemetry during heat exposure...
February 27, 2018: Life Sciences
Y S Cui, Q Zhong, W F Li, Z H Liu, Y Wang, C C Hou
Objective: To investigate the effects of fluoride exposure on the thyroid hormone level and intelligence in rats and to investigate the biomarkers of intellectual impairment induced by high fluoride exposure. Methods: A total of 24 clean healthy Sprague-Dawley rats were randomly divided into control group (tap water containing 0.344 mg/L fluoride) and low-, medium-, and high-fluoride exposure groups (tap waters containing 10, 50, and 100 mg/L sodium fluoride, respectively). One male rat was cohabited with two female rats in the same group...
December 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
Prabir Kumar Chakraborty, Brennah Murphy, Soumyajit Banerjee Mustafi, Anindya Dey, Xunhao Xiong, Geeta Rao, Sarwat Naz, Min Zhang, Da Yang, Danny N Dhanasekaran, Resham Bhattacharya, Priyabrata Mukherjee
Deregulation of mitochondrial morphogenesis, a dynamic equilibrium between mitochondrial fusion and fission processes, is now evolving as a key metabolic event that fuels tumor growth and therapy resistance. However, fundamental knowledge underpinning how cancer cells reprogram mitochondrial morphogenesis remains incomplete. Here, we report that cystathionine β-synthase (CBS) reprograms mitochondrial morphogenesis in ovarian cancer (OvCa) cells by selectively regulating the stability of mitofusin 2 (MFN2)...
March 1, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Riccardo Filadi, Diana Pendin, Paola Pizzo
Mitochondria are highly dynamic organelles whose functions are essential for cell viability. Within the cell, the mitochondrial network is continuously remodeled through the balance between fusion and fission events. Moreover, it dynamically contacts other organelles, particularly the endoplasmic reticulum, with which it enterprises an important functional relationship able to modulate several cellular pathways. Being mitochondria key bioenergetics organelles, they have to be transported to all the specific high-energy demanding sites within the cell and, when damaged, they have to be efficiently removed...
February 28, 2018: Cell Death & Disease
Liming Yan, Yuanbo Qi, Xiaofang Huang, Caiting Yu, Lan Lan, Xiangyang Guo, Zihe Rao, Junjie Hu, Zhiyong Lou
Fusion of the outer mitochondrial membrane is mediated by the dynamin-like GTPase mitofusin (MFN). Here, we determined the structure of the minimal GTPase domain (MGD) of human MFN1 in complex with GDP-BeF3 - . The MGD folds into a canonical GTPase fold with an associating four-helix bundle, HB1, and forms a dimer. A potassium ion in the catalytic core engages GDP and BeF3 - (GDP-BeF3 - ). Enzymatic analysis has confirmed that efficient GTP hydrolysis by MFN1 requires potassium. Compared to previously reported MGD structures, the HB1 structure undergoes a major conformational change relative to the GTPase domains, as they move from pointing in opposite directions to point in the same direction, suggesting that a swing of the four-helix bundle can pull tethered membranes closer to achieve fusion...
February 26, 2018: Nature Structural & Molecular Biology
Jessica Sacks, Anny Mulya, Ciaran E Fealy, Hazel Huang, John D Mosinski, Mangesh R Pagadala, Hideharu Shimizu, Esam Batayyah, Philip R Schauer, Stacy A Brethauer, John P Kirwan
Bariatric surgery provides significant and durable improvements in glycemic control and hepatic steatosis, but the underlying mechanisms that drive improvements in these metabolic parameters remain to be fully elucidated. Recently, alterations in mitochondrial morphology have shown a direct link to nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from adult male SD rats 90-days after either Sham or RYGB surgery and continuous high-fat feeding...
February 2018: Physiological Reports
Arpita Mukherjee, Upayan Patra, Rahul Bhowmick, Mamta Chawla-Sarkar
Dynamic equilibrium between mitochondrial fission and mitochondrial fusion serves as an important quality control system within cells ensuring cellular vitality and homeostasis. Viruses often target mitochondrial dynamics as a part of their obligatory cellular reprogramming. The present study was undertaken to assess the status and regulation of mitochondrial dynamics during rotavirus (RV) infection. Distinct fragmentation of mitochondrial syncytia was observed during late hours of RV (SA11, Wa, A5-13) infection...
February 14, 2018: Cellular Microbiology
Hongzhu Yan, Chengmin Qiu, Weiwei Sun, Minmin Gu, Feng Xiao, Jue Zou, Li Zhang
Gastric cancer is the fifth most common cancer worldwide and Hippo-Yap is the novel signaling pathway which plays an important role in gastric cancer tumor development and progression. However, little insight is available to date regarding the specific role of Yes-associated protein (Yap) in gastric cancer. In the present study, we identified the mechanism through which Yap sustains gastric cancer viability and migration. Yap was greatly upregulated in gastric cancer cells and its expression promoted cellular migration and survival...
February 7, 2018: Oncology Reports
Shuichuan Huang, Zhibo Chen, Weibin Wu, Mian Wang, Rui Wang, Jin Cui, Wen Li, Shenming Wang
MicroRNA (miR)-31 serves a key role in various biological processes, including tumor development, angiogenesis and inflammation. Whether miR-31 is involved in the pathological processes of arteriosclerosis obliterans (ASO) remains to be elucidated, as does the mechanism of miR-31 regulation of arterial smooth muscle cells (ASMCs). In the present study, miR-31 expression was detected by reverse transcription-quantitative polymerase chain reaction and in situ hybridization, and was significantly upregulated in human ASO arterial walls compared with normal arterial walls (P<0...
January 2018: Experimental and Therapeutic Medicine
Gábor Koncsos, Zoltán V Varga, Tamás Baranyai, Péter Ferdinandy, Rainer Schulz, Zoltán Giricz, Kerstin Boengler
INTRODUCTION: In the heart, subsarcolemmal (SSM), interfibrillar (IFM) and perinuclear mitochondria represent three subtypes of mitochondria. The most commonly used protease during IFM isolation is the nagarse, however, its effect on the detection of mitochondrial proteins is still unclear. Therefore, we investigated whether nagarse treatment influences the quantification of mitochondrial proteins. METHODS: SSM and IFM were isolated from hearts of mice and rats...
January 26, 2018: Journal of Pharmacological and Toxicological Methods
Jiangyue Zhao, Xinwei Wu, Danhong Wu, Yinhui Yu, Yibo Yu, Yao Wang, Qiuli Fu, Jinsong Zhang, Ke Yao
Inherited mitochondrial mutations can result in mitochondrial dysfunction or stochastic oxidative damage. Cumulative mitochondrial damage is an important factor in age-related disorders, such as cataracts and macular degeneration. Mfn2 mediates the fusion of mitochondria and contribute to the dynamic balance between fusion and fission that determines mitochondria morphology. We report here that conditional loss of Mfn2 function in the head surface ectoderm leads to a range of congenital eye defects, including small, opacified lens and small eyeball in the most severe phenotypes...
January 24, 2018: Scientific Reports
Xiu-Ping Xu, Yong-Ming Yao, Guang-Ju Zhao, Zong-Sheng Wu, Jun-Cong Li, Yun-Long Jiang, Zhong-Qiu Lu, Guang-Liang Hong
BACKGROUND: Mitofusin-2 (MFN2), a well-known mitochondrial fusion protein, has been shown to participate in innate immunity, but its role in mediating adaptive immunity remains poorly characterized. In this study, we explored the potential role of MFN2 in mediating the immune function of T lymphocytes. METHODS: We manipulated MFN2 gene expression in Jurkat cells via lentiviral transduction of MFN2 small interfering RNA (siRNA) or full-length MFN2. After transduction, the immune response and its underlying mechanism were determined in Jurkat cells...
February 5, 2018: Chinese Medical Journal
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