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https://www.readbyqxmd.com/read/29351413/mitochondrial-content-is-preserved-throughout-disease-progression-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-regardless-of-taurine-supplementation
#1
Robert G Barker, Victoria L Wyckelsma, Hongyang Xu, Robyn M Murphy
Mitochondrial dysfunction is a pathological feature of Duchenne muscular Dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterised by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP and involved in Ca2+ regulation and apoptotic signalling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28d which stabilises after 8 weeks. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29348146/the-ins-and-outs-of-mitofusins
#2
Marta Giacomello, Luca Scorrano
Mitofusins are outer membrane proteins essential for mitochondrial fusion. Their accepted topology posits that both N and C termini face the cytoplasm. In this issue, Mattie et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201611194) demonstrate instead that their C termini reside in the intermembrane space. These findings call for a revision of the current models of mitochondrial fusion.
January 18, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29323106/sequential-forward-and-reverse-transport-of-the-na-ca2-exchanger-generates-ca2-oscillations-within-mitochondria
#3
Krishna Samanta, Gary R Mirams, Anant B Parekh
Mitochondrial Ca2+ homoeostasis regulates aerobic metabolism and cell survival. Ca2+ flux into mitochondria is mediated by the mitochondrial calcium uniporter (MCU) channel whereas Ca2+ export is often through an electrogenic Na+-Ca2+ exchanger. Here, we report remarkable functional versatility in mitochondrial Na+-Ca2+ exchange under conditions where mitochondria are depolarised. Following physiological stimulation of cell-surface receptors, mitochondrial Na+-Ca2+ exchange initially operates in reverse mode, transporting cytosolic Ca2+ into the matrix...
January 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29290623/identification-of-new-activators-of-mitochondrial-fusion-reveals-a-link-between-mitochondrial-morphology-and-pyrimidine-metabolism
#4
Laia Miret-Casals, David Sebastián, José Brea, Eva M Rico-Leo, Manuel Palacín, Pedro M Fernández-Salguero, M Isabel Loza, Fernando Albericio, Antonio Zorzano
Mitochondria are dynamic organelles that produce most of the cellular ATP, and are involved in many other cellular functions such as Ca2+ signaling, differentiation, apoptosis, cell cycle, and cell growth. One key process of mitochondrial dynamics is mitochondrial fusion, which is catalyzed by mitofusins (MFN1 and MFN2) and OPA1. The outer mitochondrial membrane protein MFN2 plays a relevant role in the maintenance of mitochondrial metabolism, insulin signaling, and mutations that cause neurodegenerative disorders...
December 23, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29237928/correlations-between-mitofusin-2-expression-in-fibroblasts-and-pelvic-organ-prolapse-an-in-vitro-study
#5
Ye Lu, Hua-Yun Chen, Xiao-Qing Wang, Jing-Xue Wang
BACKGROUND: Both Mitofusin 2 (Mfn2) and pelvic organ prolapse (POP) are related to aging. The aim of the present study was to investigate the variations of Mfn2 expression in the uterosacral ligaments of patients with and/or without POP and their correlations with the expression of procollagen. METHODS: Fibroblasts were cultured using tissue specimens that were harvested from the uterosacral ligaments of POP and non-POP (NPOP) patients (n = 10 for each group) from September 2016 to December 2016...
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29234100/a-bi-fluorescence-complementation-system-to-detect-associations-between-the-endoplasmic-reticulum-and-mitochondria
#6
Mark Harmon, Philip Larkman, Giles Hardingham, Mandy Jackson, Paul Skehel
Close contacts between the endoplasmic reticulum membrane and the mitochondrial outer membrane facilitate efficient transfer of lipids between the organelles and coordinate Ca2+ signalling and stress responses. Changes to this coupling is associated with a number of metabolic disorders and neurodegenerative diseases including Alzheimer's, Parkinson's and motor neuron disease. The distance between the two membranes at regions of close apposition is below the resolution of conventional light microscopy, which makes analysis of these interactions challenging...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29215305/cerebrovascular-function-and-mitochondrial-bioenergetics-after-ischemia-reperfusion-in-male-rats
#7
Ibolya Rutkai, Ivan Merdzo, Sanjay V Wunnava, Genevieve T Curtin, Prasad Vg Katakam, David W Busija
The underlying factors promoting increased mitochondrial proteins, mtDNA, and dilation to mitochondrial-specific agents in male rats following tMCAO are not fully elucidated. Our goal was to determine the morphological and functional effects of ischemia/reperfusion (I/R) on mitochondria using electron microscopy, Western blot, mitochondrial oxygen consumption rate (OCR), and Ca2+ sparks activity measurements in middle cerebral arteries (MCAs) from male Sprague Dawley rats (Naïve, tMCAO, Sham). We found a greatly increased OCR in ipsilateral MCAs (IPSI) compared with contralateral (CONTRA), Sham, and Naïve MCAs...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29212658/a-new-mitofusin-topology-places-the-redox-regulated-c-terminus-in-the-mitochondrial-intermembrane-space
#8
Sevan Mattie, Jan Riemer, Jeremy G Wideman, Heidi M McBride
Mitochondrial fusion occurs in many eukaryotes, including animals, plants, and fungi. It is essential for cellular homeostasis, and yet the underlying mechanisms remain elusive. Comparative analyses and phylogenetic reconstructions revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from one another and lack strong sequence similarity. Bioinformatic analysis showed that fungal Fzo1 proteins exhibit two predicted transmembrane domains, whereas metazoan Mitofusins contain only a single transmembrane domain...
December 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29210177/mitochondrial-fission-promotes-cell-migration-by-ca2-camkii-erk-fak-pathway-in-hepatocellular-carcinoma
#9
Xiacheng Sun, Haiyan Cao, Lei Zhan, Chun Yin, Gang Wang, Ping Liang, Jibin Li, Zhe Wang, Bingrong Liu, Qichao Huang, Jinliang Xing
BACKGROUND AND AIMS: Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumor cells remained largely unknown. METHODS: In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of HCC cells...
December 6, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29189636/mitochondrial-fusion-and-fission-proteins-and-the-recognition-memory-of-imprinting-in-domestic-chicks
#10
Giorgi Margvelani, Maia Meparishvili, Ekaterine Tevdoradze, Brian J McCabe, Revaz Solomonia
Visual imprinting is a learning process through which young, visually naive animals come to recognize a visual stimulus by being exposed to it (training) and subsequently approach the stimulus in preference to others. A large body of evidence indicates that a restricted part of the forebrain, the intermediate medial mesopallium (IMM), is a memory region for visual imprinting in the domestic chick. Previous studies have shown learning-related up-regulation of several mitochondrial proteins in the IMM 24 h after training...
November 17, 2017: Neuroreport
https://www.readbyqxmd.com/read/29178074/beyond-deubiquitylation-usp30-mediated-regulation-of-mitochondrial-homeostasis
#11
Jiayun Hou, Mohmmad Eldeeb, Xiangdong Wang
Mutations or sequence aberrations in the Parkin gene are among the most common causes of autosomal recessive Parkinson's disorder (PD). Parkin, a cytoplasmic E3 ubiquitin ligase, is involved in mitochondrial quality control pathways, including mitochondrial fission and mitophagy by autophagy-related genes. Parkin mediates the covalent addition of ubiquitin (Ub) chains to Lys 6, Lys 11, and Lys 63 on diverse mitochondrial-related target proteins. USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29174633/regulation-of-innate-immune-functions-by-guanylate-binding-proteins
#12
REVIEW
Gerrit J K Praefcke
Guanylate-binding proteins (GBP) are a family of dynamin-related large GTPases which are expressed in response to interferons and other pro-inflammatory cytokines. GBPs mediate a broad spectrum of innate immune functions against intracellular pathogens ranging from viruses to bacteria and protozoa. Several binding partners for individual GBPs have been identified and several different mechanisms of action have been proposed depending on the organisms, the cell type and the pathogen used. Many of these anti-pathogenic functions of GBPs involve the recruitment to and the subsequent destruction of pathogen containing vacuolar compartments, the assembly of large oligomeric innate immune complexes such as the inflammasome, or the induction of autophagy...
November 2, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29158819/pro-inflammatory-cxcr3-impairs-mitochondrial-function-in-experimental-non-alcoholic-steatohepatitis
#13
Jinghua Du, Xiang Zhang, Juqiang Han, Kwan Man, Yanquan Zhang, Eagle Sh Chu, Yuemin Nan, Jun Yu
Mitochondrial dysfunction plays a crucial role in the development of non-alcoholic steatohepatitis (NASH). However, the regulator of mitochondrial dysfunction in the pathogenesis of NASH is still largely unclear. CXCR3 is an essential pro-inflammatory factor in chronic liver diseases. We explored the significance of CXCR3 in regulating mitochondrial function during NASH development in animal models and cultured hepatocytes. METHODS: The effects of CXCR3 on mitochondrial function were evaluated by genetic knockout or pharmacological inhibition in mouse models and in vitro...
2017: Theranostics
https://www.readbyqxmd.com/read/29125827/early-cerebellar-deficits-in-mitochondrial-biogenesis-and-respiratory-chain-complexes-in-the-kiko-mouse-model-of-friedreich-ataxia
#14
Hong Lin, Jordi Magrane, Amy Rattelle, Anna Stepanova, Alexander Galkin, Elisia M Clark, Yi Na Dong, Sarah M Halawani, David R Lynch
Friedreich ataxia (FRDA), the most common recessive inherited ataxia, results from deficiency of frataxin, a small mitochondrial protein crucial for iron-sulphur cluster formation and ATP production. Frataxin deficiency is associated with mitochondrial dysfunction in FRDA patients and animal models; however, early mitochondrial pathology in FRDA cerebellum remains elusive. Using frataxin knock-in/knockout (KIKO) mice and KIKO mice carrying the mitoDendra transgene, we show early cerebellar deficits in mitochondrial biogenesis and respiratory chain complexes in this FRDA model...
November 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29097872/mitofusin-2-mediated-mitochondrial-ca-2-uptake-1-2-induced-liver-injury-in-rat-remote-ischemic-perconditioning-liver-transplantation-and-alpha-mouse-liver-12-hypoxia-cell-line-models
#15
Ruo-Peng Liang, Jun-Jun Jia, Jian-Hui Li, Ning He, Yan-Fei Zhou, Li Jiang, Tao Bai, Hai-Yang Xie, Lin Zhou, Yu-Ling Sun
AIM: To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS: Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR...
October 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29093165/sequences-flanking-the-transmembrane-segments-facilitate-mitochondrial-localization-and-membrane-fusion-by-mitofusin
#16
Xiaofang Huang, Xin Zhou, Xiaoyu Hu, Amit S Joshi, Xiangyang Guo, Yushan Zhu, Quan Chen, William A Prinz, Junjie Hu
Mitochondria constantly divide and fuse. Homotypic fusion of the outer mitochondrial membranes requires the mitofusin (MFN) proteins, a family of dynamin-like GTPases. MFNs are anchored in the membrane by transmembrane (TM) segments, exposing both the N-terminal GTPase domain and the C-terminal tail (CT) to the cytosol. This arrangement is very similar to that of the atlastin (ATL) GTPases, which mediate fusion of endoplasmic reticulum (ER) membranes. We engineered various MFN-ATL chimeras to gain mechanistic insight into MFN-mediated fusion...
November 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29068134/structure-function-and-regulation-of-mitofusin-2-in-health-and-disease
#17
Gursimran Chandhok, Michael Lazarou, Brent Neumann
Mitochondria are highly dynamic organelles that constantly migrate, fuse, and divide to regulate their shape, size, number, and bioenergetic function. Mitofusins (Mfn1/2), optic atrophy 1 (OPA1), and dynamin-related protein 1 (Drp1), are key regulators of mitochondrial fusion and fission. Mutations in these molecules are associated with severe neurodegenerative and non-neurological diseases pointing to the importance of functional mitochondrial dynamics in normal cell physiology. In recent years, significant progress has been made in our understanding of mitochondrial dynamics, which has raised interest in defining the physiological roles of key regulators of fusion and fission and led to the identification of additional functions of Mfn2 in mitochondrial metabolism, cell signalling, and apoptosis...
October 25, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29034772/opa-interacting-protein-5-modulates-docetaxel-induced-cell-death-via-regulation-of-mitophagy-in-gastric-cancer
#18
Tae Woo Kim, Seon-Jin Lee, Young-Jun Park, Sang Yoon Park, Byung Moo Oh, Yun Sun Park, Bo-Yeon Kim, Young-Ha Lee, Hee Jun Cho, Suk Ran Yoon, Yong-Kyung Choe, Hee Gu Lee
Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29028772/heme-oxygenase-1-protects-the-liver-from-septic-injury-by-modulating-tlr4-mediated-mitochondrial-quality-control-in-mice
#19
Jin-Sook Park, Hyo-Sun Choi, So-Yeon Yim, Sun-Mee Lee
Mitochondrial dysfunction is involved in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome (MODS). Mitochondrial quality control (QC) is characterized by self-recovering mitochondrial damage through mitochondrial biogenesis, mitophagy, and fission/fusion. Heme oxygenase (HO)-1 acts as a signaling molecule to modulate inflammation. The present study elucidated the cytoprotective mechanisms of HO-1 in sepsis, particularly focusing on toll-like receptor (TLR)4-mediated mitochondrial QC. Mice were subjected to sepsis by cecal ligation and puncture (CLP)...
October 12, 2017: Shock
https://www.readbyqxmd.com/read/28993979/methamphetamine-augments-concurrent-astrocyte-mitochondrial-stress-oxidative-burden-and-antioxidant-capacity-tipping-the-balance-in-hiv-associated-neurodegeneration
#20
Kathleen Borgmann, Anuja Ghorpade
Methamphetamine (METH) use, with and without human immunodeficiency virus (HIV)-1 comorbidity, exacerbates neurocognitive decline. Oxidative stress is a probable neurotoxic mechanism during HIV-1 central nervous system infection and METH abuse, as viral proteins, antiretroviral therapy and METH have each been shown to induce mitochondrial dysfunction. However, the mechanisms regulating mitochondrial homeostasis and overall oxidative burden in astrocytes are not well understood in the context of HIV-1 infection and METH abuse...
October 9, 2017: Neurotoxicity Research
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