The Experts below are selected from a list of 141654 Experts worldwide ranked by ideXlab platform
Hugo W Moser - One of the best experts on this subject based on the ideXlab platform.
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peroxisome Biogenesis disorders
Biochimica et Biophysica Acta, 2006Co-Authors: Steven J Steinberg, Gabriele Dodt, Nancy Braverman, Gerald V Raymond, Ann B Moser, Hugo W MoserAbstract:Defects in PEX genes impair peroxisome assembly and multiple metabolic pathways confined to this organelle, thus providing the biochemical and molecular bases of the peroxisome Biogenesis disorders (PBD). PBD are divided into two types—Zellweger syndrome spectrum (ZSS) and rhizomelic chondrodysplasia punctata (RCDP). Biochemical studies performed in blood and urine are used to screen for the PBD. DNA testing is possible for all of the disorders, but is more challenging for the ZSS since 12 PEX genes are known to be associated with this spectrum of PBD. In contrast, PBD-RCDP is associated with defects in the PEX7 gene alone. Studies of the cellular and molecular defects in PBD patients have contributed significantly to our understanding of the role of each PEX gene in peroxisome assembly.
Xi Long - One of the best experts on this subject based on the ideXlab platform.
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A mutation in porcine pre-miR-15b alters the Biogenesis of MiR-15b\16-1 cluster and strand selection of MiR-15b.
PloS one, 2017Co-Authors: Wenyang Sun, Jinjie Qiu, Zonggang Luo, Jiugang Zhao, Tinghuan Zhang, Jing Lan, Jinyong Wang, Mingzhou Li, Lei Chen, Xi LongAbstract:MicroRNAs (miRNAs) are small non-coding RNAs that are involved in translational regulation of the messenger RNA molecules. Sequence variations in the genes encoding miRNAs could influence their Biogenesis and function. MiR-15b plays an important role in cellular proliferation, apoptosis and the cell cycle. Here, we report the identification of a C58T mutation in porcine pre-miR-15b. Through in vitro and in vivo experiments, we determined that this mutation blocks the transition from pri-miRNA to pre-miRNA, alters the strand selection between miR-15b-5p and miR-15b-3p, and obstructs Biogenesis of the downstream miR-16-1. These results serve to highlight the importance of miRNA mutations and their impacts on miRNA Biogenesis.
Wenyang Sun - One of the best experts on this subject based on the ideXlab platform.
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A mutation in porcine pre-miR-15b alters the Biogenesis of MiR-15b\16-1 cluster and strand selection of MiR-15b.
PloS one, 2017Co-Authors: Wenyang Sun, Jinjie Qiu, Zonggang Luo, Jiugang Zhao, Tinghuan Zhang, Jing Lan, Jinyong Wang, Mingzhou Li, Lei Chen, Xi LongAbstract:MicroRNAs (miRNAs) are small non-coding RNAs that are involved in translational regulation of the messenger RNA molecules. Sequence variations in the genes encoding miRNAs could influence their Biogenesis and function. MiR-15b plays an important role in cellular proliferation, apoptosis and the cell cycle. Here, we report the identification of a C58T mutation in porcine pre-miR-15b. Through in vitro and in vivo experiments, we determined that this mutation blocks the transition from pri-miRNA to pre-miRNA, alters the strand selection between miR-15b-5p and miR-15b-3p, and obstructs Biogenesis of the downstream miR-16-1. These results serve to highlight the importance of miRNA mutations and their impacts on miRNA Biogenesis.
James Brugarolas - One of the best experts on this subject based on the ideXlab platform.
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multistep regulation of tfeb by mtorc1
Autophagy, 2017Co-Authors: Silvia Vegarubindecelis, Samuel Penallopis, Meghan Konda, James BrugarolasAbstract:ABSTRACTThe master regulator of lysosome Biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEBS211A localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1. Here, we report that endogenous TFEB is phosphorylated at S122 in an MTORC1-dependent manner, that S122 is phosphorylated in vitro by recombinant MTOR, and that S122 is important for TFEB regulation by MTORC1. Specifically, nuclear localization following MTORC1 inhibition is blocked by a S122D mutation (despite S211 dephosphorylation). Furthermore, such a mutation inhibits lysosomal Biogenesis induced by Torin1. These data reveal a novel mechanism of TFEB regulation by MTORC1 essential for lysosomal Biogenesis.
Gerald I Shulman - One of the best experts on this subject based on the ideXlab platform.
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Regulation of mitochondrial Biogenesis
Essays in Biochemistry, 2010Co-Authors: François R Jornayvaz, Gerald I ShulmanAbstract:Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) is a co-transcriptional regulation factor that induces mitochondrial Biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1α itself is regulated by several different key factors involved in mitochondrial Biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial Biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial Biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial Biogenesis and function may provide potentially important novel therapeutic targets.
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amp kinase is required for mitochondrial Biogenesis in skeletal muscle in response to chronic energy deprivation
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Haihong Zong, Lawrence H Young, Marc Pypaert, James Mu, Morris J Birnbaum, Gerald I ShulmanAbstract:Mitochondrial Biogenesis is a critical adaptation to chronic energy deprivation, yet the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved fuel sensor, in mitochondrial Biogenesis we studied transgenic mice expressing a dominant-negative mutant of AMPK in muscle (DN-AMPK). Both DN-AMPK and WT mice were treated with β-guanidinopropionic acid (GPA), a creatine analog, which led to similar reductions in the intramuscular ATP/AMP ratio and phosphocreatine concentrations. In WT mice, GPA treatment resulted in activation of muscle AMPK and mitochondrial Biogenesis. However, the same GPA treatment in DN-AMPK mice had no effect on AMPK activity or mitochondrial content. Furthermore, AMPK inactivation abrogated GPA-induced increases in the expression of peroxisome proliferator-activated receptor γ coactivator 1α and calcium/calmodulin-dependent protein kinase IV (both master regulators of mitochondrial Biogenesis). These data demonstrate that by sensing the energy status of the muscle cell, AMPK is a critical regulator involved in initiating mitochondrial Biogenesis.