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Mitochondrial dynamics

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https://www.readbyqxmd.com/read/28636943/opa1-isoforms-in-the-hierarchical-organization-of-mitochondrial-functions
#1
Valentina Del Dotto, Prashant Mishra, Sara Vidoni, Mario Fogazza, Alessandra Maresca, Leonardo Caporali, J Michael McCaffery, Martina Cappelletti, Enrico Baruffini, Guy Lenaers, David Chan, Michela Rugolo, Valerio Carelli, Claudia Zanna
OPA1 is a GTPase that controls mitochondrial fusion, cristae integrity, and mtDNA maintenance. In humans, eight isoforms are expressed as combinations of long and short forms, but it is unclear whether OPA1 functions are associated with specific isoforms and/or domains. To address this, we expressed each of the eight isoforms or different constructs of isoform 1 in Opa1(-/-) MEFs. We observed that any isoform could restore cristae structure, mtDNA abundance, and energetic efficiency independently of mitochondrial network morphology...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28634072/mitochondrial-dynamics-coordinate-cell-differentiation
#2
Masafumi Noguchi, Atsuko Kasahara
Cells differentiate into specific and functional lineages to build up tissues. It has been shown in several tissues that mitochondrial morphology, levels of "mitochondrial shaping" proteins, and mitochondrial functions change upon differentiation. In this review, we highlight the significance of mitochondrial dynamics and functions in tissue development, cell differentiation, and reprogramming processes. Signalling cascades are critical for tissue stem cell maintenance and cell fate determination, and growing evidence demonstrates mitochondria could act as a centre of intra and extracellular signals to coordinate signalling pathways, such as Notch, Wnt, and YAP/TAZ signalling...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#3
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/28630277/t-cell-intracellular-antigens-and-hu-antigen-r-antagonistically-modulate-mitochondrial-activity-and-dynamics-by-regulating-optic-atrophy-1-gene-expression
#4
Isabel Carrascoso, José Alcalde, Carmen Sánchez-Jiménez, Paloma González-Sánchez, José M Izquierdo
Mitochondria undergo frequent morphological changes to control their function. We show here that T-cell intracellular antigens (TIA1b/TIARb) and Hu antigen R (HuR) have antagonistic roles in mitochondrial function by modulating the expression of mitochondrial shaping proteins. Expression of TIA1b/TIARb alters the mitochondrial dynamic network by enhancing fission and clustering, which is accompanied by a decrease in respiration. By contrast, HuR expression promotes fusion and cristae remodeling and increases respiratory activity...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28629773/bering-the-burden-of-damage-pathway-crosstalk-and-posttranslational-modification-of-base-excision-repair-proteins-regulate-dna-damage-management
#5
REVIEW
Kristin L Limpose, Anita H Corbett, Paul W Doetsch
DNA base damage and non-coding apurinic/apyrimidinic (AP) sites are ubiquitous types of damage that must be efficiently repaired to prevent mutations. These damages can occur in both the nuclear and mitochondrial genomes. Base excision repair (BER) is the frontline pathway for identifying and excising damaged DNA bases in both of these cellular compartments. Recent advances demonstrate that BER does not operate as an isolated pathway but rather dynamically interacts with components of other DNA repair pathways to modulate and coordinate BER functions...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28628337/buckling-under-pressure-curvature-based-lipid-segregation-and-stability-modulation-in-cardiolipin-containing-bilayers
#6
Kevin J Boyd, Nathan N Alder, Eric R May
Mitochondrial metabolic function is affected by the morphology and protein organization of the mitochondrial inner membrane (MIM). Cardiolipin (CL) is a unique tetra-acyl lipid that is involved in the maintenance of the highly-curved shape of the MIM as well as spatial organization of the proteins necessary for respiration and oxidative phosphorylation. Cardiolipin has been suggested to self-organize into lipid domains due to its inverted conical molecular geometry, though the driving forces for this organization are not fully understood...
June 19, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28628083/molecular-basis-of-selective-mitochondrial-fusion-by-heterotypic-action-between-opa1-and-cardiolipin
#7
Tadato Ban, Takaya Ishihara, Hiroto Kohno, Shotaro Saita, Ayaka Ichimura, Katsumi Maenaka, Toshihiko Oka, Katsuyoshi Mihara, Naotada Ishihara
Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. Optic atrophy 1 (OPA1) is an essential GTPase protein for both mitochondrial inner membrane (IM) fusion and cristae morphology. Under mitochondria-stress conditions, membrane-anchored L-OPA1 is proteolytically cleaved to form peripheral S-OPA1, leading to the selection of damaged mitochondria for mitophagy. However, molecular details of the selective mitochondrial fusion are less well understood. Here, we showed that L-OPA1 and cardiolipin (CL) cooperate in heterotypic mitochondrial IM fusion...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28622510/microbial-genetic-composition-tunes-host-longevity
#8
Bing Han, Priya Sivaramakrishnan, Chih-Chun J Lin, Isaiah A A Neve, Jingquan He, Li Wei Rachel Tay, Jessica N Sowa, Antons Sizovs, Guangwei Du, Jin Wang, Christophe Herman, Meng C Wang
Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPR(mt)) in the host...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622501/microbiome-and-longevity-gut-microbes-send-signals-to-host-mitochondria
#9
Jan Gruber, Brian K Kennedy
The microbiome has emerged as a major determinant of the functioning of host organisms, affecting both health and disease. Here, Han et al. use the workhorse of aging research, C. elegans, to identify specific mechanisms by which gut bacteria influence mitochondrial dynamics and aging, a first step toward analogous manipulations to modulate human aging.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28621306/targeted-two-photon-chemical-apoptotic-ablation-of-defined-cell-types-in-vivo
#10
Robert A Hill, Eyiyemisi C Damisah, Fuyi Chen, Alex C Kwan, Jaime Grutzendler
A major bottleneck limiting understanding of mechanisms and consequences of cell death in complex organisms is the inability to induce and visualize this process with spatial and temporal precision in living animals. Here we report a technique termed two-photon chemical apoptotic targeted ablation (2Phatal) that uses focal illumination with a femtosecond-pulsed laser to bleach a nucleic acid-binding dye causing dose-dependent apoptosis of individual cells without collateral damage. Using 2Phatal, we achieve precise ablation of distinct populations of neurons, glia and pericytes in the mouse brain and in zebrafish...
June 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28615318/miro1-mediated-mitochondrial-positioning-shapes-intracellular-energy-gradients-required-for-cell-migration
#11
Max-Hinderk Schuler, Agnieszka Lewandowska, Giuseppe Di Caprio, Wesley Skillern, Srigokul Upadhyayula, Tom Kirchhausen, Janet M Shaw, Brian Cunniff
It has long been postulated, though never directly demonstrated that mitochondria are strategically positioned in the cytoplasm to meet local requirements for energy production. Here we show that positioning of mitochondria in mouse embryonic fibroblasts (MEFs) determines the shape of intracellular energy gradients in living cells. Specifically, the ratio of ATP to ADP was highest at perinuclear areas of dense mitochondria and gradually declined approaching more peripheral sites. Furthermore, the majority of mitochondria were positioned at the ventral surface of the cell, correlating with high ATP:ADP ratios close to the ventral membrane that rapidly decreased towards the dorsal surface...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28615291/high-affinity-cooperative-ca-2-binding-by-micu1-micu2-serves-as-an-on-off-switch-for-the%C3%A2-uniporter
#12
Kimberli J Kamer, Zenon Grabarek, Vamsi K Mootha
The mitochondrial calcium uniporter is a Ca(2+)-activated Ca(2+) channel that is essential for dynamic modulation of mitochondrial function in response to cellular Ca(2+) signals. It is regulated by two paralogous EF-hand proteins-MICU1 and MICU2, but the mechanism is unknown. Here, we demonstrate that both MICU1 and MICU2 are stabilized by Ca(2+) We reconstitute the MICU1-MICU2 heterodimer and demonstrate that it binds Ca(2+) cooperatively with high affinity. We discover that both MICU1 and MICU2 exhibit affinity for the mitochondria-specific lipid cardiolipin...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#13
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28611221/optogenetic-control-of-mitochondrial-metabolism-and-ca-2-signaling-by-mitochondria-targeted-opsins
#14
Tatiana Tkatch, Elisa Greotti, Gytis Baranauskas, Diana Pendin, Soumitra Roy, Luliaoana I Nita, Jennifer Wettmarshausen, Matthias Prigge, Ofer Yizhar, Orian S Shirihai, Daniel Fishman, Michal Hershfinkel, Ilya A Fleidervish, Fabiana Perocchi, Tullio Pozzan, Israel Sekler
Key mitochondrial functions such as ATP production, Ca(2+) uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH(+)) across the inner membrane. Although several drugs can modulate ΔμH(+), their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells...
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28609725/new-insights-on-mitochondrial-heterogeneity-observed-in-prepared-mitochondrial-samples-following-a-method-for-freeze-fracture-and-scanning-electron-microscopy
#15
Julie A MacDonald, William H Fowle, Dori C Woods PhD
Mitochondria are dynamic intracellular organelles with diverse roles in tissue- and cell type-specific processes, extending beyond bioenergetics. In keeping with this array of functions, mitochondria are described as heterogeneous both between and within tissue types based on multiple parameters, including a broad spectrum of morphological features, and new research points toward a need for the evaluation of mitochondria as isolated organelles. Although transmission electron microscopy (TEM) is commonly used for the evaluation of mitochondria in tissues and renders mitochondrial structures in ultra-thin sections in two-dimensions, additional information regarding complex features within these organelles can be ascertained using scanning electron microscopy (SEM), which allows for analysis of phenotypic differences in three-dimensions...
June 1, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28608965/hydrogen-sulphide-modulating-mitochondrial-morphology-to-promote-mitophagy-in-endothelial-cells-under-high-glucose-and-high-palmitate
#16
Ning Liu, Jichao Wu, Linxue Zhang, Zhaopeng Gao, Yu Sun, Miao Yu, Yajun Zhao, Shiyun Dong, Fanghao Lu, Weihua Zhang
Endothelial cell dysfunction is one of the main reasons for type II diabetes vascular complications. Hydrogen sulphide (H2 S) has antioxidative effect, but its regulation on mitochondrial dynamics and mitophagy in aortic endothelial cells under hyperglycaemia and hyperlipidaemia is unclear. Rat aortic endothelial cells (RAECs) were treated with 40 mM glucose and 200 μM palmitate to imitate endothelium under hyperglycaemia and hyperlipidaemia, and 100 μM NaHS was used as an exogenous H2 S donor. Firstly, we demonstrated that high glucose and palmitate decreased H2 S production and CSE expression in RAECs...
June 13, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28607632/mitochondrial-transfer-from-wharton-s-jelly-mesenchymal-stem-cell-to-merrf-cybrid-reduces-oxidative-stress-and-improves-mitochondrial-bioenergetics
#17
Yao-Chung Chuang, Chia-Wei Liou, Shang-Der Chen, Pei-Wen Wang, Jiin-Haur Chuang, Mao-Meng Tiao, Te-Yao Hsu, Hung-Yu Lin, Tsu-Kung Lin
Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a maternally inherited mitochondrial disease affecting neuromuscular functions. Mt.8344A>G mutation in mitochondrial DNA (mtDNA) is the most common cause of MERRF syndrome and has been linked to an increase in reactive oxygen species (ROS) level and oxidative stress, as well as impaired mitochondrial bioenergetics. Here, we tested whether WJMSC has therapeutic potential for the treatment of MERRF syndrome through the transfer of mitochondria...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28607103/dynamin-related-protein-1-inhibition-attenuates-cardiovascular-calcification-in-the-presence-of-oxidative-stress
#18
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/28607005/opa1-deficiency-promotes-secretion-of-fgf21-from-muscle-that-prevents-obesity-and-insulin-resistance
#19
Renata Oliveira Pereira, Satya M Tadinada, Frederick M Zasadny, Karen Jesus Oliveira, Karla Maria Pereira Pires, Angela Olvera, Jennifer Jeffers, Rhonda Souvenir, Rose Mcglauflin, Alec Seei, Trevor Funari, Hiromi Sesaki, Matthew J Potthoff, Christopher M Adams, Ethan J Anderson, E Dale Abel
Mitochondrial dynamics is a conserved process by which mitochondria undergo repeated cycles of fusion and fission, leading to exchange of mitochondrial genetic content, ions, metabolites, and proteins. Here, we examine the role of the mitochondrial fusion protein optic atrophy 1 (OPA1) in differentiated skeletal muscle by reducing OPA1 gene expression in an inducible manner. OPA1 deficiency in young mice results in non-lethal progressive mitochondrial dysfunction and loss of muscle mass. Mutant mice are resistant to age- and diet-induced weight gain and insulin resistance, by mechanisms that involve activation of ER stress and secretion of fibroblast growth factor 21 (FGF21) from skeletal muscle, resulting in increased metabolic rates and improved whole-body insulin sensitivity...
June 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28606861/the-molecular-characterizations-of-cu-znsod-and-mnsod-and-its-responses-of-mrna-expression-and-enzyme-activity-to-aeromonas-hydrophila-or-lipopolysaccharide-challenge-in-qihe-crucian-carp-carassius-auratus
#20
Xianghui Kong, Dan Qiao, Xianliang Zhao, Li Wang, Jie Zhang, Dandan Liu, Hongxu Zhang
Superoxide dismutases (SODs), as the prime antioxidant enzymes, present the first line of defense against oxidative stress caused by excessive reactive oxygen species (ROS) in organism. In the study, two distinct members of SOD family were cloned and analyzed in Qihe crucian carp Carassius auratus (designated as CaCu/ZnSOD and CaMnSOD, respectively). The full-length cDNA of CaCu/ZnSOD is 759 bp, containing a 5' -untranslated region (UTR) of 39 bp, a ORF (including stop codon, TAG) of 465 bp and a 3'-UTR of 255 bp...
June 9, 2017: Fish & Shellfish Immunology
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