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https://www.readbyqxmd.com/read/27903607/mitochondrial-division-occurs-concurrently-with-autophagosome-formation-but-independently-of-drp1-during-mitophagy
#1
Shun-Ichi Yamashita, Xiulian Jin, Kentaro Furukawa, Maho Hamasaki, Akiko Nezu, Hidenori Otera, Tetsu Saigusa, Tamotsu Yoshimori, Yasuyoshi Sakai, Katsuyoshi Mihara, Tomotake Kanki
Mitophagy is thought to play an important role in mitochondrial quality control. Mitochondrial division is believed to occur first, and autophagosome formation subsequently occurs to enwrap mitochondria as a process of mitophagy. However, there has not been any temporal analysis of mitochondrial division and autophagosome formation in mitophagy. Therefore, the relationships among these processes remain unclear. We show that the mitochondrial division factor Dnm1 in yeast or Drp1 in mammalian cells is dispensable for mitophagy...
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27903605/a-dividing-matter-drp1-dnm1-independent-mitophagy
#2
Martin Graef
Whether or not mitophagy depends on prior mitochondrial fragmentation by the canonical mitochondrial division machinery is controversial. In this issue, Yamashita et al. (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201605093) report that mitochondrial fragments start to bud and divide from mitochondrial tubules when in tight association with forming autophagosomes, but independently of the mitochondrial division factor Drp1/Dnm1.
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27889639/sulforaphane-is-a-nrf2-independent-inhibitor-of-mitochondrial-fission
#3
Gary B O'Mealey, William L Berry, Scott M Plafker
The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN), an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1) cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1...
November 21, 2016: Redox Biology
https://www.readbyqxmd.com/read/27889468/mitochondrial-cristae-remodelling-is-associated-with-disrupted-opa1-oligomerisation-in-the-huntington-s-disease-r6-2-fragment-model
#4
Tanja Hering, Kerstin Kojer, Nathalie Birth, Jaqueline Hallitsch, Jan-Willem Taanman, Michael Orth
There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27889261/nik-map3k14-regulates-mitochondrial-dynamics-and-trafficking-to-promote-cell-invasion
#5
Ji-Ung Jung, Sowndharya Ravi, Dong W Lee, Kassandra McFadden, Michael L Kamradt, L Gerard Toussaint, Raquel Sitcheran
Although the role of NF-κB-inducing kinase (NIK) in immunity is well established, its relevance in cancer is just emerging. Here we describe novel functions for NIK in regulating mitochondrial dynamics and motility to promote cell invasion. We show that NIK is localized to mitochondria in cancer cell lines, ex vivo tumor tissue, and mouse embryonic fibroblasts (MEFs). NIK promotes mitochondrial fission, velocity, and directional migration, resulting in subcellular distribution of mitochondria to the periphery of migrating cells...
November 15, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27862231/early-stage-functions-of-mitochondrial-autophagy-and-oxidative-stress-in-acetaminophen-induced-liver-injury
#6
Yan Gao, Shifeng Chu, Zhao Zhang, Wei Zuo, Congyuan Xia, Qidi Ai, Piao Luo, Peng Cao, Naihong Chen
Mitochondria go through frequent cycles of fusion and fission, a process required for mitochondrial quality control by eliminating ROS-damaged mitochondria through mitochondrial autophagy. Acetaminophen (APAP) overdose can cause liver injury in animals and human beings by inducing mitochondrial damage, which need to be further evaluated. The aim of the current study is to assess the changes between oxidative damage and mitophagy in vivo and in vitro, which mimics APAP-induced liver injury (AILI) in humans. Liver damage was monitored by measuring the levels of biochemical indexes...
November 9, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27858084/a-threshold-of-transmembrane-potential-is-required-for-mitochondrial-dynamic-balance-mediated-by-drp1-and-oma1
#7
Edith Jones, Norma Gaytan, Iraselia Garcia, Alan Herrera, Manuel Ramos, Divya Agarwala, Maahrose Rana, Wendy Innis-Whitehouse, Erin Schuenzel, Robert Gilkerson
As an organellar network, mitochondria dynamically regulate their organization via opposing fusion and fission pathways to maintain bioenergetic homeostasis and contribute to key cellular pathways. This dynamic balance is directly linked to bioenergetic function: loss of transmembrane potential across the inner membrane (Δψ m) disrupts mitochondrial fission/fusion balance, causing fragmentation of the network. However, the level of Δψ m required for mitochondrial dynamic balance, as well as the relative contributions of fission and fusion pathways, have remained unclear...
November 17, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27852062/disrupted-in-schizophrenia-1-disc1-inhibits-glioblastoma-development-by-regulating-mitochondria-dynamics
#8
Xingchun Gao, Yajing Mi, Na Guo, Zhifang Hu, Fengrui Hu, Dou Liu, Lei Gao, Xingchun Gou, Weilin Jin
Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27847271/oleuropein-improves-mitochondrial-function-to-attenuate-oxidative-stress-by-activating-the-nrf2-pathway-in-the-hypothalamic-paraventricular-nucleus-of-spontaneously-hypertensive-rats
#9
Wenyan Sun, Xin Wang, Chen Hou, Liang Yang, Hongbao Li, Jing Guo, Chanjuan Huo, Molin Wang, Yuwang Miao, Jiankang Liu, Yuming Kang
Hypertension is associated with increased reactive oxygen species (ROS) production in the paraventricular nucleus (PVN) of the hypothalamus. Oleuropein (OL) has a variety of biochemical roles, including antihypertensive and antioxidative functions. However, there have been few reports on the effects of OL on oxidative stress in the PVN on hypertension. In spontaneously hypertensive rats (SHR), eight-week administration of 60 mg/kg/day of OL significantly reduced blood pressure, pro-inflammatory cytokines and the expression of components of the renin-angiotensin system (RAS) compared with SHR rats treated with saline...
November 12, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27844171/mitochondrial-dynamics-as-a-therapeutic-target-for-treating-cardiac-diseases
#10
Sang-Bing Ong, Derek J Hausenloy
Mitochondria are dynamic in nature and are able to shift their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins - mitofusins 1 and 2 (Mfn1 and 2), and optic atrophy 1 (Opa1) as well as the mitochondrial fission proteins - dynamin-related peptide 1 (Drp1) and fission protein 1 (Fis1). Despite having a unique spatial arrangement, cardiac mitochondria have been implicated in a variety of disorders including ischemia-reperfusion injury (IRI), heart failure, diabetes, and pulmonary hypertension...
November 15, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27837193/intact-initiation-of-autophagy-and-mitochondrial-fission-by-acute-exercise-in-skeletal-muscle-of-patientswith-type-2-diabetes
#11
Rikke Kruse, Andreas J T Pedersen, Jonas M Kristensen, Stine J Petersson, Jørgen F P Wojtaszewski, Kurt Højlund
AIMS: Type 2 diabetes (T2D) is characterized by insulin resistance, mitochondrial dysregulation, and, in some studies, exercise resistance in skeletal muscle. Regulation of autophagy and mitochondrial dynamics during exercise and recovery is important for skeletal muscle homeostasis, and these responses may be altered in T2D. MATERIALS AND METHODS: We examined the effect of acute exercise on markers of autophagy and mitochondrial fusion and fission in skeletal muscle biopsies from patients with T2D (n=13) and weight-matched controls (n=14) before, immediately after and 3h after an acute bout of exercise...
November 11, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27833818/sevoflurane-postconditioning-attenuates-cardiomyocyte-hypoxia-reoxygenation-injury-via-restoring-mitochondrial-morphology
#12
Jin Yu, Jianjiang Wu, Peng Xie, Yiliyaer Maimaitili, Jiang Wang, Zhengyuan Xia, Feng Gao, Xing Zhang, Hong Zheng
BACKGROUND: Anesthetic postconditioning is a cellular protective approach whereby exposure to a volatile anesthetic renders a tissue more resistant to subsequent ischemic/reperfusion event. Sevoflurane postconditioning (SPostC) has been shown to exert cardioprotection against ischemia/reperfusion injury, but the underlying mechanism is unclear. We hypothesized that SPostC protects cardiomyocytes against hypoxia/reoxygenation (H/R) injury by maintaining/restoring mitochondrial morphological integrity, a critical determinant of cell fate...
2016: PeerJ
https://www.readbyqxmd.com/read/27831567/erk-drp1-dependent-mitochondrial-fission-is-involved-in-the-msc-induced-drug-resistance-of-t-cell-acute-lymphoblastic-leukemia-cells
#13
Jianye Cai, Jiancheng Wang, Yinong Huang, Haoxiang Wu, Ting Xia, Jiaqi Xiao, Xiaoyong Chen, Hongyu Li, Yuan Qiu, Yingnan Wang, Tao Wang, Huimin Xia, Qi Zhang, Andy Peng Xiang
The bone marrow microenvironment facilitates the proliferation and survival of leukemia cells, contributing to disease relapse. Bone marrow-derived mesenchymal stem cells (MSCs) are well known to promote cancer chemoresistance via soluble factors and cell adhesion. However, little is known about the effects of MSCs on the mitochondrial dynamics of T-cell acute lymphoblastic leukemia (T-ALL) cells, or how this may influence the chemoresistance of these cells. Here, we tested both indirect (Transwell) and direct coculture strategies, and found that MSCs protected T-ALL cells from chemotherapeutic cell death and cytotoxicity under both culture conditions...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27830583/dynamin-related-protein-1-drp1-mediating-mitophagy-contributes-to-the-pathophysiology-of-nervous-system-diseases-and-brain-injury
#14
REVIEW
Qiong Wu, Cheng-Liang Luo, Lu-Yang Tao
As the main source of energy (celluar ATP) in eukaryotic cells, mitochondria are involved in cellular physiology and pathology. The balance of mitochondrial dynamic, fission and fusion regulated by quality control mechanisms, provides a guarantee for maintaining mitochondrial function, even celluar function. Worn out mitochondria would be removed through mitophagy which is regulated by autophagy related proteins and mitochondrial membrane proteins. Drp1, dynamic-related protein 1, is regarded as one of the most important proteins to evaluate mitochondrial fission mediating mitophagy in neurodegenerative diseases (eg...
November 10, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27822712/dynasore-improves-motor-function-recovery-via-inhibition-of-neuronal-apoptosis-and-astrocytic-proliferation-after-spinal-cord-injury-in-rats
#15
Gang Li, Feifei Shen, Zhongkai Fan, Yangsong Wang, Xiangquan Kong, Deshui Yu, Xiaodong Zhi, Gang Lv, Yang Cao
Spinal cord injury (SCI) is a common and devastating central nervous system insult which lacks efficient treatment. Our previous experimental findings indicated that dynamin-related protein 1 (Drp1) mediates mitochondrial fission during SCI, and inhibition of Drp1 plays a significant protective effect after SCI in rats. Dynasore inhibits GTPase activity at both the plasma membrane (dynamin 1, 2) and the mitochondria membrane (Drp1). The aim of the present study was to investigate the beneficial effects of dynasore on SCI and its underlying mechanism in a rat model...
November 7, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27816895/dengue-virus-induces-mitochondrial-elongation-through-impairment-of-drp1-triggered-mitochondrial-fission
#16
Vincent Barbier, Diane Lang, Sierra Valois, Alan L Rothman, Carey L Medin
Mitochondria are highly dynamic organelles that undergo continuous cycles of fission and fusion to maintain essential cellular functions. An imbalance between these two processes can result in many pathophysiological outcomes. Dengue virus (DENV) interacts with cellular organelles, including mitochondria, to successfully replicate in cells. This study used live-cell imaging and found an increase in mitochondrial length and respiration during DENV infection. The level of mitochondrial fission protein, Dynamin-related protein 1 (Drp1), was decreased on mitochondria during DENV infection, as well as Drp1 phosphorylated on serine 616, which is important for mitochondrial fission...
January 2017: Virology
https://www.readbyqxmd.com/read/27815660/mitochondrial-phosphatase-pgam5-regulates-keap1-mediated-bcl-xl-degradation-and-controls-cardiomyocyte-apoptosis-driven-by-myocardial-ischemia-reperfusion-injury
#17
Chen Yang, Xiaojuan Liu, Fangfang Yang, Weixun Zhang, Zihao Chen, Daliang Yan, Qingsheng You, Xiang Wu
Phosphoglycerate mutase 5 (PGAM5) is a mitochondrial membrane protein that plays crucial roles in necroptosis and apoptosis. Though PGAM5 is known to be required for inducing intrinsic apoptosis through interacting with BCL2 associated X protein (Bax) and dynamin-related protein 1 (Drp1), the expression and role of PGAM5 in cardiomyocyte apoptosis driven by myocardial ischemia/reperfusion injury(MIRI) has not been studied. The present study shows that PGAM5 expression decreased after MIRI in vivo, positively correlated with Bcl-xL expression, negatively correlated with Kelch-ECH associating protein 1 (Keap1) expression...
November 4, 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27810362/imbalance-of-mitochondrial-dynamics-in-drosophila-models-of-amyotrophic-lateral-sclerosis
#18
Volodya Altanbyek, Sun-Joo Cha, Ga-Un Kang, Dai Sig Im, Seongsoo Lee, Hyung-Jun Kim, Kiyoung Kim
Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease, characterized by progressive and selective loss of motor neurons in the brain and spinal cord. DNA/RNA-binding proteins such as TDP-43, FUS, and TAF15 have been linked with the sporadic and familial forms of ALS. However, the exact pathogenic mechanism of ALS is still unknown. Recently, we found that ALS-causing genes such as TDP-43, FUS, and TAF15 genetically interact with mitochondrial dynamics regulatory genes. In this study, we show that mitochondrial fission was highly enhanced in muscles and motor neurons of TDP-43, FUS, and TAF15-induced fly models of ALS...
October 31, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27802433/targeting-dynamin-2-as-a-novel-pathway-to-inhibit-cardiomyocyte-apoptosis-following-oxidative-stress
#19
Danchen Gao, Jian Yang, Yutao Wu, Qiwen Wang, Qiaoling Wang, En Yin Lai, Jianhua Zhu
BACKGROUND/AIMS: Inhibition of Drp-1-mediated mitochondrial fission limits reactive oxygen species (ROS) production and apoptosis in cardiomyocytes subjected to ischemia/reperfusion injury. It remains unknown if Dynamin 2 inhibition results in similar protective effects. Here we studied the role of Dynamin 2 in cardiomyocyte oxidative stress-induced apoptosis and ROS production. METHODS: The effect of lentiviral shRNA (lv5-shRNA) mediated Dynamin 2 knockdown on apopotosis, mitochondria, and ROS production were studied in neonatal mouse cardiomycytes, which were further treated with either selective Drp1 inhibitor mdivi-1 or the Dynamin 2/Drp1 inhibitor Dynasore...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27801666/overexpression-of-pkm2-promotes-mitochondrial-fusion-through-attenuated-p53-stability
#20
Haili Wu, Peng Yang, Wanglai Hu, Yingying Wang, Yangxu Lu, Lichao Zhang, Yongsheng Fan, Hong Xiao, Zhuoyu Li
M2-type pyruvate kinase (PKM2) contributes to the Warburg effect. However, it remains unknown as to whether PKM2 has an inhibitory effect on mitochondrial function. We report in this work that PKM2 overexpression inhibits the expression of Drp1 and results in the mitochondrial fusion. The ATP production was found to be decreased, the mtDNA copy number elevated and the expression level of electron transport chain (ETC) complex I, III, V depressed in PKM2 overexpressed cells. PKM2 overexpression showed a decreased p53 protein level and a shorter p53 half-life...
October 27, 2016: Oncotarget
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