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https://www.readbyqxmd.com/read/28644713/an-unstructured-loop-that-is-critical-for-interactions-of-the-stalk-domain-of-drp1-with-saturated-phosphatidic-acid
#1
Yoshihiro Adachi, Miho Iijima, Hiromi Sesaki
Dynamin-related protein 1 (Drp1) is a dynamin superfamily GTPase, which drives membrane constriction during mitochondrial division. To mediate mitochondrial division, Drp1 is recruited to the mitochondrial outer membrane and is assembled into the division machinery. We previously showed that Drp1 interacts with phosphatidic acid (PA) and saturated phospholipids in the mitochondrial membrane, and this interaction restrains Drp1 in initiating the constriction of mitochondria. Here, we show that the role of saturated acyl chains of phospholipids is independent of their contribution to the membrane curvature or lipid packing suggesting their direct interaction with Drp1...
June 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28641287/chrysophanol-suppressed-glutamate-induced-hippocampal-neuronal-cell-death-via-regulation-of-dynamin-related-protein-1-dependent-mitochondrial-fission
#2
Unbin Chae, Ju-Sik Min, Hyun Hee Leem, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Chrysophanic acid, or chrysophanol, is an anthraquinone found in Rheum palmatum, which was used in the preparation of oriental medicine in ancient China. The hippocampus plays a major role in controlling the activities of the short- and long-term memory. It is one of the major regions affected by excessive cell death in Alzheimer's disease. Therefore, neuronal cell-death modulation in the hippocampus is important for maintaining neuronal function. We investigated chrysophanol's effects on glutamate-induced hippocampal neuronal cell death...
June 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28634116/succinate-induced-neuronal-mitochondrial-fission-and-hexokinase-ii-malfunction-in-ischemic-stroke-therapeutical-effects-of-kaempferol
#3
Bin Wu, Hong Luo, Xu Zhou, Cai-Yi Cheng, Lin Lin, Bao-Lin Liu, Kang Liu, Ping Li, Hua Yang
Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury...
June 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#4
Kaustuv Basu, Driss Lajoie, Tristan Aumentado-Armstrong, Jin Chen, Roman I Koning, Blaise Bossy, Mihnea Bostina, Attila Sik, Ella Bossy-Wetzel, Isabelle Rouiller
Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers...
2017: PloS One
https://www.readbyqxmd.com/read/28630156/apoptotic-foci-at-mitochondria-in-and-around-bax-pores
#5
REVIEW
Begoña Ugarte-Uribe, Ana J García-Sáez
The permeabilization of the mitochondrial outer membrane by Bax and Bak during apoptosis is considered a key step and a point of no return in the signalling pathway. It is always closely related to the reorganization of mitochondrial cristae that frees cytochrome c to the intermembrane space and to massive mitochondrial fragmentation mediated by the dynamin-like protein Drp1. Despite multiple evidence in favour of a functional link between these processes, the molecular mechanisms that connect them and their relevance for efficient apoptosis signalling remain obscure...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28624623/mitochondrial-fission-forms-a-positive-feedback-loop-with-cytosolic-calcium-signaling-pathway-to-promote-autophagy-in-hepatocellular-carcinoma-cells
#6
Qichao Huang, Haiyan Cao, Lei Zhan, Xiacheng Sun, Gang Wang, Jibin Li, Xu Guo, Tingting Ren, Zhe Wang, Yinghua Lyu, Bingrong Liu, Jiaze An, Jinliang Xing
Both mitochondrial morphology and the level of cytosolic calcium [Ca(2+)]c are actively changed and play critical roles in a number of malignancies. However, whether communications existed between these two processes to ingeniously control the malignant phenotype are far from clear. We investigated the reciprocal regulation between mitochondrial fission and cytosolic calcium signaling in human hepatocellular carcinoma (HCC) cells. Furthermore, the underlying molecular mechanisms and the synergistic effect on autophagy were explored...
June 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28623750/lcz696-improves-cardiac-function-via-alleviating-drp1-mediated-mitochondrial-dysfunction-in-mice-with-doxorubicin-induced-dilated-cardiomyopathy
#7
Yan Xia, Zhangwei Chen, Ao Chen, Mingqiang Fu, Zhen Dong, Kai Hu, Xiangdong Yang, Yunzeng Zou, Aijun Sun, Juying Qian, Junbo Ge
AIMS: LCZ696, a novel angiotensin receptor neprilysin inhibitor, is effective in treating heart failure patients. Doxorubicin (DOX) is an effective antitumor medication but the cardiotoxicity limited its clinical use. In this study, we aimed to determine the effect of LCZ696 on DOX-induced cardiomyopathy in mice and in vitro and to explore related mechanisms focusing on fission protein dynamin-related protein 1 (Drp1). METHODS AND RESULTS: In human study, we found that myocardial fission protein Drp1 expression and its ser 616 phosphorylation were significantly increased in dilated cardiomyopathy (DCM) patients...
June 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28607103/dynamin-related-protein-1-inhibition-attenuates-cardiovascular-calcification-in-the-presence-of-oxidative-stress
#8
Maximillian Rogers, Natalia Maldonado-Martinez, Joshua D Hutcheson, Claudia Goettsch, Shinji Goto, Iwao Yamada, Tyler Faits, Hiromi Sesaki, Masanori Aikawa, Elena Aikawa
Rationale: Mitochondrial changes occur during cell differentiation and cardiovascular disease. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs. Objective: To examine the effects of osteogenic promoting conditions on DRP1, and whether DRP1 inhibition alters the development of cardiovascular calcification. Methods and Results: DRP1 was enriched in calcified regions of human carotid arteries, examined by immunohistochemistry...
June 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28606997/hpv-e7-induces-chemotherapy-mediated-tumor-suppression-by-ceramide-dependent-mitophagy
#9
Raquela J Thomas, Natalia Oleinik, Shanmugam Panneer Selvam, Silvia G Vaena, Mohammed Dany, Rose N Nganga, Ryan Depalma, Kyla D Baron, Jisun Kim, Zdzislaw M Szulc, Besim Ogretmen
Human papillomavirus (HPV) infection is linked to improved survival in response to chemo-radiotherapy for patients with oropharynx head and neck squamous cell carcinoma (HNSCC). However, mechanisms involved in increased HNSCC cell death by HPV signaling in response to therapy are largely unknown. Here, using molecular, pharmacologic and genetic tools, we show that HPV early protein 7 (E7) enhances ceramide-mediated lethal mitophagy in response to chemotherapy-induced cellular stress in HPV-positive HNSCC cells by selectively targeting retinoblastoma protein (RB)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28602540/deficiencies-in-mitochondrial-dynamics-sensitize-caenorhabditis-elegans-to-arsenite-and-other-mitochondrial-toxicants-by-reducing-mitochondrial-adaptability
#10
Anthony L Luz, Tewodros R Godebo, Latasha L Smith, Tess C Leuthner, Laura L Maurer, Joel N Meyer
Mitochondrial fission, fusion, and mitophagy are interlinked processes that regulate mitochondrial shape, number, and size, as well as metabolic activity and stress response. The fundamental importance of these processes is evident in the fact that mutations in fission (DRP1), fusion (MFN2, OPA1), and mitophagy (PINK1, PARK2) genes can cause human disease (collectively >1/10,000). Interestingly, however, the age of onset and severity of clinical manifestations varies greatly between patients with these diseases (even those harboring identical mutations), suggesting a role for environmental factors in the development and progression of certain mitochondrial diseases...
June 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28598422/constriction-of-the-mitochondrial-inner-compartment-is-a-priming-event-for-mitochondrial-division
#11
Bongki Cho, Hyo Min Cho, Youhwa Jo, Hee Dae Kim, Myungjae Song, Cheil Moon, Hyongbum Kim, Kyungjin Kim, Hiromi Sesaki, Im Joo Rhyu, Hyun Kim, Woong Sun
Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated. Here we report spontaneous and repetitive constriction of mitochondrial inner compartment (CoMIC) associated with subsequent division in neurons...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28596240/control-of-mitochondrial-homeostasis-by-endocytic-regulatory-proteins
#12
Trey Farmer, James B Reinecke, Shuwei Xie, Kriti Bahl, Naava Naslavsky, Steve Caplan
Mitochondria play essential roles in cellular energy processes, including ATP production, control of ROS, and apoptosis. While mitochondrial function is regulated by the dynamics of fusion and fission, mitochondrial homeostasis remains incompletely understood. Recent studies implicate Dynamin-2 and dynamin-related protein-1 (Drp1), as GTPases involved in mitochondrial fission. We identify the ATPase and endocytic protein, EHD1, as a novel regulator of mitochondrial fission. EHD1-depletion induces a static and elongated network of mitochondria in the cell...
June 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28591721/ginkgolide-k-attenuates-neuronal-injury-after-ischemic-stroke-by-inhibiting-mitochondrial-fission-and-gsk-3%C3%AE-dependent-increases-in-mitochondrial-membrane-permeability
#13
Xu Zhou, Hui-Ying Wang, Bin Wu, Cai-Yi Cheng, Wei Xiao, Zhen-Zhong Wang, Yu-Yu Yang, Ping Li, Hua Yang
Ginkgolide K (GK) belongs to the ginkgolide family of natural compounds found in Ginkgo biloba leaves, which have been used for centuries to treat cerebrovascular and cardiovascular diseases. We evaluated the protective effects of GK against neuronal apoptosis by assessing its ability to sustain mitochondrial integrity and function. Co-immunoprecipitation showed that Drp1 binding to GSK-3β was increased after an oxygen-glucose deprivation/reperfusion (OGD/R) insult in cultured neuroblastoma cells. This induced Drp1 and GSK-3β translocation to mitochondria and mitochondrial dysfunction, which was attenuated by GK...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590414/mtdna-as-a-mediator-for-expression-of-hypoxia-inducible-factor-1%C3%AE-and-ros-in-hypoxic-neuroblastoma-cells
#14
Chung-Wen Kuo, Meng-Han Tsai, Tsu-Kung Lin, Mao-Meng Tiao, Pei-Wen Wang, Jiin-Haur Chuang, Shang-Der Chen, Chia-Wei Liou
Mitochondria consume O₂ to produce ATP and are critical for adaption of hypoxia, but the role of mitochondria in HIF-1α pathway is as yet unclear. In this study, mitochondrial DNA (mtDNA) enriched (SK-N-AS) and depleted (ρ⁰) cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) were measured. The results showed that hypoxia-stimulated exposure elevated expression of HIF-1α, which was additionally influenced by level of generated ROS within the cytosol...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28579326/rip1-rip3-drp1-pathway-regulates-nlrp3-inflammasome-activation-following-subarachnoid-hemorrhage
#15
Keren Zhou, Ligen Shi, Zhen Wang, Jingyi Zhou, Anatol Manaenko, Cesar Reis, Sheng Chen, Jianmin Zhang
The NLRP3 inflammasome functions as a crucial component of the inflammatory response in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the activation of NLRP3 inflammasome has not been well elucidated. In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection...
June 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28577890/exercise-training-protects-against-aging-induced-mitochondrial-fragmentation-in-mouse-skeletal-muscle-in-a-pgc-1%C3%AE-dependent-manner
#16
Jens Frey Halling, Stine Ringholm, Jesper Olesen, Clara Prats, Henriette Pilegaard
Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effects of aging and exercise training on mitochondrial network structure remain unclear. This study examined the effects of aging and exercise training on mitochondrial network structure using confocal microscopy on mitochondria-specific stains in single muscle fibers from PGC-1α KO and WT mice...
May 31, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28560384/hydrogen-sulfide-inhibits-mitochondrial-fission-in-neuroblastoma-n2a-cells-through-the-drp1-erk1-2-signaling-pathway
#17
Peifeng Qiao, Fengli Zhao, Mengjie Liu, Dan Gao, Hua Zhang, Yong Yan
Hydrogen sulfide (H2S) has been demonstrated to have various effects on mitochondrial function. The aim of the present study was to investigate the effects of H2S on mitochondrial fission and the potential underlying mechanisms of these effects. Transmission electron microscopy analysis demonstrated that sodium hydrosulfide (NaHS, a donor of H2S) inhibited mitochondrial fission in a dose‑ and time‑dependent manner. Treating neuro‑2a (N2a) mouse neuroblastoma cells with 400 µM NaHS for 16 h significantly increased the % of elongated mitochondria and reduced the number of mitochondria per cell compared with untreated cells...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28552593/tyrphostin-a9-improves-blastocyst-development-in-porcine-embryos-through-induction-of-dynamin-related-protein-1-dependent-mitochondrial-fission
#18
Jae-Hyun Ahn, Hyo-Jin Park, Jin-Woo Kim, Jae-Young Park, Soo-Yong Park, Seul-Gi Yang, Chang-Hyun Kim, Seung-Bin Yoon, Sun-Uk Kim, Kyu-Tae Chang, Deog-Bon Koo
Mitochondrial dynamics are associated with the development of porcine embryos. However, little is known about the effects of mitochondrial dynamics-related genes (Drp1 and pDrp1-Ser616) on early porcine embryo development. Here, we investigated the effect of Drp1-dependent mitochondrial fission signaling on the development of porcine embryos using the mitochondrial fission inducer, tyrphostin A9 (TA9). We determined that TA9 (1μM) treated embryos were increased the mitochondrial functions, blastocyst development rate and quality, as well as decreased mitochondria-specific superoxide and mitochondrial apoptosis...
May 26, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28548464/control-of-cell-death-and-mitochondrial-fission-by-erk1-2-map-kinase-signalling
#19
REVIEW
Simon J Cook, Kate Stuart, Rebecca Gilley, Matthew J Sale
The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions...
May 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28536949/exercise-and-doxorubicin-treatment-modulate-cardiac-mitochondrial-quality-control-signaling
#20
I Marques-Aleixo, E Santos-Alves, J R Torrella, P J Oliveira, J Magalhães, A Ascensão
The cross-tolerance effect of exercise against heart mitochondrial-mediated quality control, remodeling and death-related mechanisms associated with sub-chronic Doxorubicin (DOX) treatment is yet unknown. We therefore analyzed the effects of two distinct chronic exercise models (endurance treadmill training-TM and voluntary free wheel activity-FW) performed during the course of the sub-chronic DOX treatment on mitochondrial susceptibility to permeability transition pore (mPTP), apoptotic and autophagic signaling and mitochondrial dynamics...
May 23, 2017: Cardiovascular Toxicology
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