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491.
Edith Jones Norma Gaytan Iraselia Garcia Alan Herrera Manuel Ramos Divya Agarwala Maahrose Rana Wendy Innis-Whitehouse Erin Schuenzel Robert Gilkerson 《Cellular and molecular life sciences : CMLS》2017,74(7):1347-1363
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. To explore this, mitochondrial morphology and Δψ m were examined via confocal imaging and tetramethyl rhodamine ester (TMRE) flow cytometry, respectively, in cultured 143B osteosarcoma cells. When normalized to the TMRE value of untreated 143B cells as 100%, both genetic (mtDNA-depleted ρ0) and pharmacological [carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-treated] cell models below 34% TMRE fluorescence were unable to maintain mitochondrial interconnection, correlating with loss of fusion-active long OPA1 isoforms (L-OPA1). Mechanistically, this threshold is maintained by mechanistic coordination of DRP1-mediated fission and OPA1-mediated fusion: cells lacking either DRP1 or the OMA1 metalloprotease were insensitive to loss of Δψ m, instead maintaining an obligately fused morphology. Collectively, these findings demonstrate a mitochondrial ‘tipping point’ threshold mediated by the interaction of Δψ m with both DRP1 and OMA1; moreover, DRP1 appears to be required for effective OPA1 maintenance and processing, consistent with growing evidence for direct interaction of fission and fusion pathways. These results suggest that Δψ m below threshold coordinately activates both DRP1-mediated fission and OMA1 cleavage of OPA1, collapsing mitochondrial dynamic balance, with major implications for a range of signaling pathways and cellular life/death events. 相似文献
492.
493.
Helgadottir A Thorleifsson G Magnusson KP Grétarsdottir S Steinthorsdottir V Manolescu A Jones GT Rinkel GJ Blankensteijn JD Ronkainen A Jääskeläinen JE Kyo Y Lenk GM Sakalihasan N Kostulas K Gottsäter A Flex A Stefansson H Hansen T Andersen G Weinsheimer S Borch-Johnsen K Jorgensen T Shah SH Quyyumi AA Granger CB Reilly MP Austin H Levey AI Vaccarino V Palsdottir E Walters GB Jonsdottir T Snorradottir S Magnusdottir D Gudmundsson G Ferrell RE Sveinbjornsdottir S Hernesniemi J Niemelä M Limet R 《Nature genetics》2008,40(2):217-224
Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases. 相似文献
494.
Khaja R Zhang J MacDonald JR He Y Joseph-George AM Wei J Rafiq MA Qian C Shago M Pantano L Aburatani H Jones K Redon R Hurles M Armengol L Estivill X Mural RJ Lee C Scherer SW Feuk L 《Nature genetics》2006,38(12):1413-1418
Numerous types of DNA variation exist, ranging from SNPs to larger structural alterations such as copy number variants (CNVs) and inversions. Alignment of DNA sequence from different sources has been used to identify SNPs and intermediate-sized variants (ISVs). However, only a small proportion of total heterogeneity is characterized, and little is known of the characteristics of most smaller-sized (<50 kb) variants. Here we show that genome assembly comparison is a robust approach for identification of all classes of genetic variation. Through comparison of two human assemblies (Celera's R27c compilation and the Build 35 reference sequence), we identified megabases of sequence (in the form of 13,534 putative non-SNP events) that were absent, inverted or polymorphic in one assembly. Database comparison and laboratory experimentation further demonstrated overlap or validation for 240 variable regions and confirmed >1.5 million SNPs. Some differences were simple insertions and deletions, but in regions containing CNVs, segmental duplication and repetitive DNA, they were more complex. Our results uncover substantial undescribed variation in humans, highlighting the need for comprehensive annotation strategies to fully interpret genome scanning and personalized sequencing projects. 相似文献
495.
用人工饲料:CAR、ARA、ARA、ARA2、DHA、CD和活饵;蓝藻粉(Spirulina)、中肋骨条藻(Skeletomemacostatum)、扁藻(Tetraselmischuii)和卤虫(Artemia)分别在取自实验室供水系统和自然海区的海水中喂养印度对虾(Penaeusiducus)幼体。结果表明,投喂鲜活铒的印度对虾幼体,在取自实室供水系统的海水中,平均成活率是55%,在取自自然海 相似文献