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PINK1 and Parkin to control mitochondria remodeling
Koh, Hyongjong,Chung, Jongkyeong Korean Association of Anatomists 2010 Anatomy & Cell Biology Vol.43 No.3
<P>Parkinson's disease (PD), one of the most common neurodegenerative diseases, is characterized by movement disorders and a loss of dopaminergic (DA) neurons. PD mainly occurs sporadically, but may also result from genetic mutations in several PD-linked genes. Recently, genetic studies with <I>Drosophila</I> mutants, <I>parkin</I> and <I>PINK1</I>, two common PD-associated genes, demonstrated that Parkin acts downstream of PINK1 in maintaining mitochondrial function and integrity. Further studies revealed that PINK1 translocates Parkin to mitochondria and regulates critical mitochondrial remodeling processes. These findings, which suggest that mitochondrial dysfunction is a prominent cause of PD pathogenesis, provide valuable insights which may aid in the development of effective treatments for PD.</P>
PINK₁ and Parkin to control mitochondria remodeling
Hyongjong Koh,Jongkyeong Chung 대한해부학회 2010 Anatomy & Cell Biology Vol.43 No.3
Parkinson’s disease (PD), one of the most common neurodegenerative diseases, is characterized by movement disorders and a loss of dopaminergic (DA) neurons. PD mainly occurs sporadically, but may also result from genetic mutations in several PD-linked genes. Recently, genetic studies with Drosophila mutants, parkin and PINK₁, two common PD-associated genes, demonstrated that Parkin acts downstream of PINK₁ in maintaining mitochondrial function and integrity. Further studies revealed that PINK1 translocates Parkin to mitochondria and regulates critical mitochondrial remodeling processes. These findings, which suggest that mitochondrial dysfunction is a prominent cause of PD pathogenesis, provide valuable insights which may aid in the development of effective treatments for PD.
BMB Reports : Perspective ; Identification of a neural pathway governing satiety in Drosophila
( Soohong Min ),( Jongkyeong Chung ) 생화학분자생물학회(구 한국생화학분자생물학회) 2016 BMB Reports Vol.49 No.3
Satiety cues a feeding animal to cease further ingestion of food, thus protecting it from excessive energy gain. Impaired control of satiety is often associated with feeding-related disorders such as obesity. In our recent study, we reported the identification of a neural pathway that expresses the myoinhibitory peptide (MIP), critical for satiety responses in Drosophila. Targeted silencing of MIP neuron activity strikingly increased the body weight (BW) through elevated food intake. Similarly, genetic disruption of the gene encoding MIP also elevated feeding and BW. Suppressing the MIP pathway behaviorally transformed the satiated flies to feed similar to the starved ones, with augmented sensitivity to food. Conversely, temporal activation of MIP neuron markedly reduced the food intake and BW, and blunted the sensitivity of the starved flies to food as if they have been satiated. Shortly after termination of MIP neuron activation, the reduced BW reverted to the normal level along with a strong feeding rebound. Together our results reveal the switch-like role of the MIP pathway in feeding regulation by controlling satiety. [BMB Reports 2016; 49(3): 137-138]
Jang, Cholsoon,Lee, Gina,Chung, Jongkyeong The Rockefeller University Press 2008 The Journal of cell biology Vol.183 No.1
<P>Silnoon (Sln) is a monocarboxylate transporter (MCT) that mediates active transport of metabolic monocarboxylates such as butyrate and lactate. Here, we identify Sln as a novel LKB1-interacting protein using <I>Drosophila melanogaster</I> genetic modifier screening. Sln expression does not affect cell cycle progression or cell size but specifically enhances LKB1-dependent apoptosis and tissue size reduction. Conversely, down-regulation of Sln suppresses LKB1-dependent apoptosis, implicating Sln as a downstream mediator of LKB1. The kinase activity of LKB1 induces apical trafficking of Sln in polarized cells, and LKB1-dependent Sln trafficking is crucial for triggering apoptosis induced by extracellular butyrate. Given that LKB1 functions to control both epithelial polarity and cell death, we propose Sln is an important downstream target of LKB1.</P>
Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the <i>Drosophila</i> Eye
Kim, Wonho,Jang, Yoon-Gu,Yang, Jinsung,Chung, Jongkyeong ELSEVIER SCIENCE B.V. AMSTERDAM 2017 DEVELOPMENTAL CELL Vol.42 No.4
<P><B>Summary</B></P> <P>Target of rapamycin complex 1 (TORC1) regulates cell growth in response to nutrients and growth factors. Although TORC1 signaling has been thoroughly studied at the cellular level, the regulation of TORC1 in multicellular tissues and organs has remained elusive. Here we found that TORC1 is selectively activated in the second mitotic wave (SMW), the terminal synchronous cell division, of the developing <I>Drosophila</I> eye. We demonstrated that Hedgehog (Hh) signaling regulates TORC1 through E2F1 and the cyclin D/Cdk4 complex in the SMW, and this regulation is independent from insulin and amino acid signaling pathways. TORC1 is necessary for the proper G1/S transition of the cells, and the activation of TORC1 rescues the cell-cycle defect of Hh signaling-deficient cells in the SMW. Based on this evolutionarily conserved regulation of TORC1 by Hh signaling, we propose that Hh-dependent developmental signaling pathways spatially regulate TORC1 activity in multicellular organisms.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TORC1 is selectively active in the second mitotic wave (SMW) of <I>Drosophila</I> eye disc </LI> <LI> Hedgehog activates TORC1 independently of insulin and amino acid signaling </LI> <LI> TORC1 regulates G1/S transition downstream of Hh signaling in the SMW </LI> <LI> TORC1 regulation by Hedgehog is conserved in mammalian cells </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
ULK1 negatively regulates Wnt signaling by phosphorylating Dishevelled
Hwang, Sun-Hong,Bang, Sunhoe,Kang, Kyung Shin,Kang, Deborah,Chung, Jongkyeong Elsevier 2019 Biochemical and biophysical research communication Vol.508 No.1
<P><B>Abstract</B></P> <P>Wnt signaling pathway plays critical roles in body axes patterning, cell fate specification, cell proliferation, cell migration, stem cell maintenance, cancer development and etc. Deregulation of this pathway can be causative of cancer, metabolic disease and neurodegenerative disease such as Parkinson`s disease. Among the core components of Wnt signaling pathway, we discovered that Dishevelled (Dsh) interacts with ULK1 and is phosphorylated by ULK1. Unexpectedly, the knockdown of ULK1 elicited a marked increase in Wnt/β-catenin signaling. Multiple ULK1 phosphorylation sites existed on Dsh and many of them were located on the PDZ-DEP region. By using evolutionarily well conserved <I>Drosophila</I> Dsh, we found that S239, S247 and S254 in the PDZ-DEP region are involved in phosphorylation of Dsh by ULK1. Among these, S247 and S254 were conserved in human Dsh. When phospho-mimetic mutants (2D and 2E Dsh mutants) of these conserved residues were generated and expressed in the eyes of the fruit flies, the activity of Dsh was significantly decreased compared to wild type Dsh. Through additional alanine scanning, we further identified that S239, S247, S254, S266, S376, S554 and S555 on full length Dsh were phosphorylated by ULK1. In regards to the S266A mutation located in the PDZ domain among these phosphorylated residues, our results suggested that Dsh forms an SDS-resistant high molecular weight complex with β-catenin and TCF in the nucleus in an S266 phosphorylation-dependent manner. Based on these results, we propose that ULK1 plays a pivotal role in the regulation of Wnt/β-catenin signaling pathway by phosphorylating Dsh.</P> <P><B>Highlights</B></P> <P> <UL> <LI> ULK1 loss-of-function cells displayed increased activation of Wnt/β-catenin signaling. </LI> <LI> ULK1 interacts with and phosphorylates Dsh. </LI> <LI> The phosphomimetic form of Dsh by ULK1 shows a decreased activity in <I>Drosophila.</I> </LI> <LI> ULK1 mobilizes Dsh from the pellet fraction to the soluble cell lysate fraction. </LI> <LI> S266A Dsh forms the high molecular weight complex with β-catenin and TCF. </LI> </UL> </P>
Kim, Wonho,Kim, Hag Dong,Jung, Youjin,Kim, Joon,Chung, Jongkyeong American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.21
<P>During animal development, various signaling pathways converge to regulate cell growth. In this study, we identified LTV1 as a novel cell growth regulator in <I>Drosophila. LTV1</I> mutant larvae exhibited developmental delays and lethality at the second larval stage. Using biochemical studies, we discovered that LTV1 interacted with ribosomal protein S3 and co-purified with free 40S ribosome subunits. We further demonstrated that LTV1 is crucial for ribosome biogenesis through 40S ribosome subunit synthesis and preribosomal RNA processing, suggesting that LTV1 is required for cell growth by regulating protein synthesis. We also demonstrated that <I>Drosophila</I> Myc (dMyc) directly regulates <I>LTV1</I> transcription and requires LTV1 to stimulate ribosome biogenesis. Importantly, the loss of <I>LTV1</I> blocked the cell growth and endoreplication induced by dMyc. Combined, these results suggest that LTV1 is a key downstream factor of dMyc-induced cell growth by properly maintaining ribosome biogenesis.</P>