Article
Biochemistry & Molecular Biology
Evrim Komurcu-Bayrak, Muhammed Abdulvahid Kalkan, Neslihan Coban, Bilge Ozsait-Selcuk, Fatih Bayrak
Summary: This study aims to investigate the effects of three missense variants of PRKAG2 on AMPK activity and found that these variations resulted in the formation of cytoplasmic glycogen deposits. Understanding the impact of PRKAG2 pathogenic variants on AMPK activity could improve the treatment and management of patients with metabolic cardiomyopathy.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Review
Cell Biology
Yohei Ohashi
Summary: Phosphatidylinositol-3-phosphate plays a crucial role in cell survival, primarily involved in autophagy and endocytic pathways. Developing highly selective drugs targeting specific VPS34/Vps34 complexes is essential for treating diseases associated with autophagy defects.
Article
Cell Biology
Zehan Hu, Devanarayanan Siva Sankar, Bich Vu, Alexandre Leytens, Christine Vionnet, Wenxian Wu, Michael Stumpe, Esther Martinez-Martinez, Bjoern Stork, Joern Dengjel
Summary: ULK1 kinase complex is a key regulator of autophagy, phosphorylating autophagy-relevant proteins for autophagosome maturation and turnover. It also interacts closely with various phosphatase complexes, such as PP2A, to coordinate protein degradation through autophagy.
Article
Multidisciplinary Sciences
Shirley Tremel, Yohei Ohashi, Dustin R. Morado, Jessie Bertram, Olga Perisic, Laura T. L. Brandt, Marie-Kristin von Wrisberg, Zhuo A. Chen, Sarah L. Maslen, Oleksiy Kovtun, Mark Skehel, Juri Rappsilber, Kathrin Lang, Sean Munro, John A. G. Briggs, Roger L. Williams
Summary: The lipid phosphatidylinositol-3-phosphate (PI3P) acts as a regulator of endocytosis and autophagy, generated by two complexes containing the lipid kinase VPS34. Rab5 and Rab1a GTPases recruit and activate specific VPS34 complexes on membranes through unique binding interfaces, guiding them to distinct cellular locations. Insights into the recruitment and activation mechanisms of VPS34 complexes by specific Rab GTPases are provided through biochemical and structural analyses.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Yu-Hsuan Chen, Tzu-Yu Huang, Yu-Tung Lin, Shu-Yu Lin, Wen-Hsin Li, Hsiang-Jung Hsiao, Ruei-Liang Yan, Hong-Wen Tang, Zhao-Qing Shen, Guang-Chao Chen, Kuen-Phon Wu, Ting-Fen Tsai, Ruey-Hwa Chen
Summary: The study reveals that branched ubiquitination of VPS34 acts as a switch between UPS and autophagy, playing an important role in lipid metabolism in the liver.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Justin M. Quiles, Rita H. Najor, Eileen Gonzalez, Monica Jeung, Wenjing Liang, Sarah M. Burbach, Erika A. Zumaya, Rachel Y. Diao, Mark A. Lampert, Asa B. Gustafsson
Summary: The degradation of macromolecules and organelles by autophagy is essential for cellular homeostasis, but it is often impaired during aging and disease. Beclin1 and Beclin2 play a role in autophagy induction, and Beclin1 is involved in regulating selective mitophagy through phosphorylation by Ulk1 in its N-terminal region.
Article
Oncology
Xiao-Wei Song, Ting Su, Bo Li, Yun-Jie Huang, Wen-Xia He, Li-Li Jiang, Chang-Jin Li, Song-Qun Huang, Song-Hua Li, Zhi-Fu Guo, Hong Wu, Bi-Li Zhang
Summary: In this study, the role of the lncRNA PRKAG2-AS in regulating the expression of PRKAG2 in cardiomyocytes was investigated. Knockdown of PRKAG2-AS in the nucleus significantly decreased the expression of PRKAG2b and PRKAG2d. PRKAG2-AS and its target genes were reduced in the hearts of patients with ischemic cardiomyopathy, suggesting a potential role in myocardial ischemia. Overexpression of PPARG, a interacting protein of PRKAG2-AS, led to an increase in PRKAG2b and PRKAG2d expression in cardiomyocytes, which could be attenuated by PRKAG2-AS knockdown. Additionally, PRKAG2-AS was elevated in hearts with dilated cardiomyopathy and its overexpression led to increased PRKAG2 expression, indicating its involvement in heart failure.
CLINICAL EPIGENETICS
(2023)
Review
Genetics & Heredity
Xue Gong, Peiyu Yu, Ting Wu, Yunru He, Kaiyu Zhou, Yimin Hua, Sha Lin, Tao Wang, He Huang, Yifei Li
Summary: This study reports two cases with PRKAG2 gene variants, presenting with different cardiac phenotypes, including cardiomyopathy and arrhythmia. The variants in the CBS and non-CBS domains of the PRKAG2 gene may contribute to the different phenotypes. Moreover, the higher expression level of PRKAG2 in the conductive tissues suggests that PRKAG2 variants may also impact the conduction system of the heart.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Cell Biology
Marina Marcelic, Hana Mahmutefendic Lucin, Antonija Jurak Begonja, Gordana Blagojevic Zagorac, Pero Lucin
Summary: This study analyzes the role of Vps34-derived PI3P in the EE recycling circuit of unperturbed cells. The results show that Vps34-derived PI3P is essential for the maturation of EEs and plays an important role in the Rab11a-dependent pathway and the biogenesis of the ERC.
Article
Food Science & Technology
Linlin Ni, Yanfeng Wei, Jingjing Pan, Xiaoyang Li, Bin Xu, Yu Deng, Tianyao Yang, Wei Liu
Summary: The study found that MeHg dose-dependently induced pathological changes, increased levels of autophagy and apoptosis in the cerebral cortex. Rapamycin pretreatment antagonized MeHg-induced apoptosis, while 3-methyladenine further aggravated apoptosis. This suggests that mTOR and Vps34 may play important roles in mediating autophagy, which in turn regulates apoptosis through MAPKs or mitochondrial apoptosis pathways.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Wenqiang Song, J. Luke Postoak, Guan Yang, Xingyi Guo, Heather H. Pua, Jackie Bader, Jeffrey C. Rathmell, Hanako Kobayashi, Volker H. Haase, Katrina L. Leaptrot, Alexandra C. Schrimpe-Rutledge, Stacy D. Sherrod, John A. McLean, Jianhua Zhang, Lan Wu, Luc Van Kaer
Summary: The lipid kinase PIK3C3 plays a crucial role in maintaining adipose tissue homeostasis and systemic metabolism. Its deficiency disrupts adipocyte autophagy and hinders adipocyte differentiation, survival, and function, leading to abnormalities in adipose tissue and the development of metabolic diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Yohei Ohashi
Summary: Macroautophagy/autophagy is triggered by various starvation and stress conditions, and essential for autophagosome formation is the phospholipid phosphatidylinositol-3-phosphate. The PIK3C3/Vps34 complex I, which includes NRBF2/Atg38 as a fifth component, plays a crucial role in autophagy initiation. With the field expanding, different conclusions have been drawn in various topics, highlighting the need for further clarification in the future.
Review
Biochemistry & Molecular Biology
Chien-An Chu, Yi-Wen Wang, Yi-Lin Chen, Hui-Wen Chen, Jing-Jing Chuang, Hong-Yi Chang, Chung-Liang Ho, Chen Chang, Nan-Haw Chow, Chung-Ta Lee
Summary: PIK3C3, as a member of the PI3K family, plays a critical role in autophagy and tumor development. Inhibition of PIK3C3 can suppress autophagy and affect tumor cell proliferation, growth, and invasion. Discovery of pharmacological inhibitors targeting PIK3C3 may provide new strategies for improving treatment outcomes in PIK3C3-mediated diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Tony Sun, Yingpu Yu, Xianfang Wu, Ashley Acevedo, Ji-Dung Luo, Jiayi Wang, William M. Schneider, Brian Hurwitz, Brad R. Rosenberg, Hachung Chung, Charles M. Rice
Summary: Defective ADAR1 editing can lead to disorders, with the two protein isoforms p150 and p110 showing different contributions to RNA editing. The challenges in expressing p150 without p110 may explain the differences in editing landscape between the two isoforms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Thomas John Mercer, Yohei Ohashi, Stefan Boeing, Harold Bj Jefferies, Stefano De Tito, Helen Flynn, Shirley Tremel, Wenxin Zhang, Martina Wirth, David Frith, Ambrosius P. Snijders, Roger Lee Williams, Sharon A. Tooze
Summary: Autophagy is regulated by ULK and VPS15 through phosphorylation, affecting the formation and activity of autophagosomes. The study reveals the crucial role of VPS15 in autophagy and its association with ULK.