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Mitochondria fission

Javier Prieto, Marian León, Xavier Ponsoda, Francisco García-García, Roque Bort, Eva Serna, Manuela Barneo-Muñoz, Francesc Palau, Joaquín Dopazo, Carlos López-García, Josema Torres
We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming...
October 18, 2016: Cell Cycle
Jia Shi, Jian-Bo Yu, Wei Liu, Dan Wang, Yuan Zhang, Li-Rong Gong, Shu-An Dong, Da-Quan Liu
Acute respiratory distress syndrome (ARDS) is one of the most devastating complications of sepsis lacking of effective therapy. Mitochondrial dynamics undergoing continuous fusion and fission play a crucial role in mitochondrial structure and function. Fis1, as a small protein located on the outer membrane of mitochondria, has been thought to be an important protein mediated mitochondrial fission. During ARDS, alveolar macrophages suffer from increased oxidative stress and apoptosis, and also accompanied by disrupted mitochondrial dynamics...
October 14, 2016: Experimental Cell Research
Huan-Yuan Chen, Dapi Meng-Lin Chiang, Zi-Jing Lin, Chia-Chun Hsieh, Gung-Chian Yin, I-Chun Weng, Peter Guttermann, Stephan Werner, Katja Henzler, Gerd Schneider, Lee-Jene Lai, Fu-Tong Liu
Mast cells play an important role in allergic responses. During activation, these cells undergo degranulation, a process by which various kinds of mediators stored in the granules are released. Granule homeostasis in mast cells has mainly been studied by electron microscopy (EM), where the fine structures of subcellular organelles are partially destroyed during sample preparation. Migration and fusion of granules have not been studied in detail in three dimensions (3D) in unmodified samples. Here, we utilized soft X-ray tomography (SXT) coupled with fluorescence microscopy to study the detailed structures of organelles during mast cell activation...
October 17, 2016: Scientific Reports
Peng Zou, Longhua Liu, Louise D Zheng, Kyle K Payne, Masoud H Manjili, Michael O Idowu, Jinfeng Zhang, Eva M Schmelz, Zhiyong Cheng
Overactive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1), was accompanied with increased mitochondrial biogenesis markers (PGC1α, NRF1, and Tfam) in breast cancer cells. However, mitochondrial number was reduced, which was associated with lower mitochondrial oxidative capacity in breast cancer cells...
2016: Oxidative Medicine and Cellular Longevity
Qilong Wang, Miao Zhang, Gloria Torres, Shengnan Wu, Changhan Ouyang, Zhonglin Xie, Ming-Hui Zou
Metformin is a widely used anti-diabetic drug that exerts cardiovascular protective effects in patients with diabetes. How metformin protects diabetes-related cardiovascular diseases remains poorly understood. Here, we show that metformin abated the progression of diabetes-accelerated atherosclerosis by inhibiting mitochondrial fission in endothelial cells.Metformin treatments markedly reduced mitochondrial fragmentation, mitigated mitochondrial-derived superoxide release, improved endothelial-dependent vasodilation, inhibited vascular inflammation, and suppressed atherosclerotic lesions in streptozotocin (STZ)-induced diabetic ApoE(-/-) mice...
October 13, 2016: Diabetes
Dan Zhao, Xiao-Man Liu, Zhong-Qiu Yu, Ling-Ling Sun, Xingchuang Xiong, Meng-Qiu Dong, Li-Lin Du
Autophagy cargos include not only soluble cytosolic materials but also bulky organelles such as ER and mitochondria. In budding yeast, two proteins that contain the PX domain and the BAR domain, Atg20/Snx42 and Atg24/Snx4, are required for organelle autophagy and contribute to general autophagy in a way that can be compensated. It remains unclear why these proteins are important for organelle autophagy. Here, we show that in a distantly related fungal organism the fission yeast Schizosaccharomyces pombe, autophagy of ER and mitochondria is induced by nitrogen starvation and is promoted by three Atg20 and Atg24 family proteins, Atg20, Atg24, and Atg24b/SPBC1711...
October 13, 2016: Journal of Cell Science
Romain Jugé, Josselin Breugnot, Célia Da Silva, Sylvie Bordes, Brigitte Closs, Abdel Aouacheria
UV irradiation is a major environmental factor causing skin dryness, aging and cancer. UVB in particular triggers cumulative DNA damage, oxidative stress and mitochondrial dysfunction. The objective of our study was to provide both qualitative and quantitative analysis of how mitochondria respond to UVB irradiation in normal human epidermal keratinocytes (NHEK) of healthy donors, with the rationale that monitoring mitochondrial shape will give an indication of cell population fitness and enable the screening of bioactive agents with UVB-protective properties...
October 12, 2016: Scientific Reports
Tianzheng Yu, Patricia Deuster, Yifan Chen
The regulation of mitochondrial morphology is closely coupled to cell survival during stress. We examined changes in the mitochondrial morphology of mouse C2C12 skeletal muscle cells in response to heat acclimation and heat shock exposure. Acclimated cells showed a greater survival rate during heat shock exposure than non-acclimated cells, and were characterized by long interconnected mitochondria and reduced expression of dynamin-related protein 1 (Drp1) for their mitochondrial fractions. Exposure of C2C12 muscle cells to heat shock led to apoptotic death featuring activation of caspase 3/7, release of cytochrome c and loss of cell membrane integrity...
October 12, 2016: Journal of Physiology
Rukmini Mukherjee, Oishee Chakrabarti
Health and homoeostasis are maintained by a dynamic balance between mitochondrial fission and fusion. Mitochondrial fusion machinery is largely unknown in mammals. Only a few reports have illustrated the role of Fzo1 in mitochondrial fusion known in Saccharomyces cerevisiae. We demonstrate that the ubiquitin ligase Mahogunin Ring Finger-1 (MGRN1) interacts with and constitutively ubiquitinates the mammalian homolog, Mitofusin1 (Mfn1) via K63 linkages. In mice models, loss of Mgrn1 function leads to severe developmental defects and adult-onset spongiform neurodegeneration, similar to prion diseases...
October 4, 2016: Biochimica et Biophysica Acta
Isabelle Duroux-Richard, Christine Roubert, Meryem Ammari, Jessy Présumey, Joachim R Grün, Thomas Häupl, Andreas Grützkau, Charles-Henri Lecellier, Valérie Boitez, Patrice Codogno, Johanna Escoubet, Yves-Marie Pers, Christian Jorgensen, Florence Apparailly
Metabolic changes drive monocyte differentiation and fate. Although abnormal mitochondria metabolism and innate immune responses participate in the pathogenesis of many inflammatory disorders, molecular events regulating mitochondrial activity to control life and death in monocytes remain poorly understood. We show here that, in the human monocytes, miR-125b attenuates the mitochondrial respiration through the silencing of the BH3-only pro-apoptotic protein BIK and promotes the elongation of mitochondrial network through the targeting of the mitochondrial fission process 1 protein MTP18, leading to apoptosis...
October 4, 2016: Blood
Carla Busquets-Cortés, Xavier Capó, Miquel Martorell, Josep A Tur, Antoni Sureda, Antoni Pons
Exercise training induces adaptations in mitochondrial metabolism, dynamics, and oxidative protection. Omega-3 fatty acids change membrane lipid composition and modulate mitochondrial function. The aim was to investigate the effect of 8-week training and docosahexaenoic acid (DHA) supplementation (1.14 g/day) on the mitochondria dynamics and antioxidant status in peripheral blood mononuclear cells (PBMCs) from sportsmen. Subjects were assigned to an intervention (N = 9) or placebo groups (N = 7) in a randomized double-blind trial...
2016: Oxidative Medicine and Cellular Longevity
Andrew S Moore, Yvette C Wong, Cory L Simpson, Erika L F Holzbaur
Mitochondria form interconnected networks that dynamically remodel in response to cellular needs. Using live-cell imaging, we investigate the role of the actin cytoskeleton in regulating mitochondrial fission and fusion. We identify cycling of actin filaments onto and off of subsets of cellular mitochondria. The association of actin filaments with mitochondrial subpopulations is transient; actin quickly disassembles, then reassembles around a distinct subpopulation, efficiently cycling through all cellular mitochondria within 14 min...
2016: Nature Communications
Jin Yu, Yiliyaer Maimaitili, Peng Xie, Jianjiang Wu, Jiang Wang, Yining Yang, Haiping Ma, Hong Zheng
AIM: Hyperglycaemia-induced cell injury is a primary cause of cardiovascular complications in diabetic patients. In vivo studies demonstrated that sevoflurane postconditioning (SpostC) was cardioprotective against ischaemia/reperfusion injury, which was blocked by hyperglycaemia. This study investigated whether high glucose concentration abrogated SpostC cardioprotection in vitro by advancing mitochondrial fission and whether mitochondrial division inhibitor-1 (Mdivi-1) restored SpostC cardioprotection in cultured primary neonatal rat cardiomyocytes (NCMs)...
September 29, 2016: Acta Physiologica
Justin Balog, Suresh L Mehta, Raghu Vemuganti
Mitochondria are dynamically active organelles, regulated through fission and fusion events to continuously redistribute them across axons, dendrites, and synapses of neurons to meet bioenergetics requirements and to control various functions, including cell proliferation, calcium buffering, neurotransmission, oxidative stress, and apoptosis. However, following acute or chronic injury to CNS, altered expression and function of proteins that mediate fission and fusion lead to mitochondrial dynamic imbalance...
September 27, 2016: Journal of Cerebral Blood Flow and Metabolism
Rostyslav Horbay, Rostyslav Bilyy
Mitochondria are the cell's power plant that must be in a proper functional state in order to produce the energy necessary for basic cellular functions, such as proliferation. Mitochondria are 'dynamic' in that they are constantly undergoing fission and fusion to remain in a functional state throughout the cell cycle, as well as during other vital processes such as energy supply, cellular respiration and programmed cell death. The mitochondrial fission/fusion machinery is involved in generating young mitochondria, while eliminating old, damaged and non-repairable ones...
September 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
Jisoo Park, Quangdon Tran, Kisun Mun, Kouhei Masuda, So Hee Kwon, Seon-Hwan Kim, Dong-Hoon Kim, George Thomas, Jongsun Park
The major biological function of mitochondria is to generate cellular energy through oxidative phosphorylation. Apart from cellular respiration, mitochondria also play a key role in signaling processes, including aging and cancer metabolism. It has been shown that S6K1-knockout mice are resistant to obesity due to enhanced beta-oxidation, with an increased number of large mitochondria. Therefore, in this report, the possible involvement of S6K1 in regulating mitochondria dynamics and function has been investigated in stable lenti-shS6K1-HeLa cells...
December 2016: Cellular Signalling
Sina Krokowski, Damián Lobato-Márquez, Serge Mostowy
Septins are cytoskeletal proteins implicated in cytokinesis and host-pathogen interactions. During macroautophagy/autophagy of Shigella flexneri, septins assemble into cage-like structures to entrap actin-polymerizing bacteria and restrict their dissemination. How septins assemble to entrap bacteria is not fully known. We discovered that mitochondria support septin cage assembly to promote autophagy of Shigella. Consistent with roles for the cytoskeleton in mitochondrial dynamics, we showed that DNM1L/DRP1 (dynamin 1 like) can interact with septins to enhance mitochondrial fission...
September 14, 2016: Autophagy
Rajagopalan Geetha, Chandrasekaran Sathiya Priya, Carani Venkatraman Anuradha
Mitochondrial abnormality is thought to play a key role in cardiac disease originating from the metabolic syndrome (MS). We evaluated the effect of troxerutin (TX), a semi-synthetic derivative of the natural bioflavanoid rutin, on the respiratory chain complex activity, oxidative stress, mitochondrial biogenesis and dynamics in heart of high fat, high fructose diet (HFFD) -induced mouse model of MS. Adult male Mus musculus mice of body weight 25-30 g were fed either control diet or HFFD for 60 days. Mice from each dietary regimen were divided into two groups on the 16(th) day and were treated or untreated with TX (150 mg/Kg bw, p...
September 14, 2016: Clinical and Experimental Pharmacology & Physiology
Anna Picca, Vito Pesce, Giuseppe Sirago, Flavio Fracasso, Christiaan Leeuwenburgh, Angela Maria Serena Lezza
Extremely interesting for aging research are those individuals able to reach older ages still with functions similar to those of younger counterparts. We examined liver samples from ad libitum-fed old (28-month-old, AL-28) and ad libitum-fed very old (32-month-old, AL-32) rats for a number of markers, relevant for mitochondrial functionality and mitochondrial DNA (mtDNA) content. As for the mtDNA content and the protein amounts of the citrate synthase and the antioxidant peroxiredoxin III there were no significant changes in the AL-32 animals...
September 13, 2016: Experimental Gerontology
Emily Filichia, Barry Hoffer, Xin Qi, Yu Luo
Accumulating evidence suggest mitochondria-mediated pathways play an important role in dopaminergic neuronal cell death in Parkinson's disease (PD). Drp1, a key regulator of mitochondrial fission, has been shown to be activated and translocated to mitochondria under stress, leading to excessive mitochondria fission and dopaminergic neuronal death in vitro. However, whether Drp1 inhibition can lead to long term stable preservation of dopaminergic neurons in PD-related mouse models remains unknown. In this study, using a classical MPTP animal PD model, we showed for the first time Drp1 activation and mitochondrial translocation in vivo after MPTP administration...
2016: Scientific Reports
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