Article
Biochemistry & Molecular Biology
Valerie Perea, Christian Cole, Justine Lebeau, Vivian Dolina, Kelsey R. Baron, Aparajita Madhavan, Jeffery W. Kelly, Danielle A. Grotjahn, R. Luke Wiseman
Summary: Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are interconnected in the development of various diseases. The PERK signaling pathway, an arm of the unfolded protein response (UPR), plays a significant role in regulating mitochondrial biology during ER stress. This study reveals that PERK activity promotes adaptive remodeling of mitochondrial membrane phosphatidic acid (PA), leading to protective mitochondrial elongation in response to acute ER stress. These findings highlight a novel role for PERK in modulating mitochondrial phospholipids and demonstrate its involvement in adapting organellar shape during ER stress.
Article
Endocrinology & Metabolism
Lili Wu, Chunfeng Liang, Xuemei Huang, Xiujun Deng, Jiming Jiang, Zuojie Luo
Summary: The study found that Sal inhibits migration and proliferation of ACC cells, increases the influx of Ca2+ ions, and promotes apoptosis. Sal treatment upregulated the expression of PERK/eIF2 alpha/ATF4 signaling-related proteins and apoptosis-related proteins. Sal reduces cell viability, increases intracellular calcium concentration, and promotes ACC cell apoptosis by activating the PERK/eIF2 alpha/ATF4 signaling pathway.
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Xiaoxin Xiang, Yanhua Zhu, Xuya Pan, Wei Xin, Jianning Chen, Weijian Tang, Ruomi Guo, Wu Yuan, Xuemin He, Li Zhou, Zhitao Ren, Siying Wen, Heting Wang, Yan Lu, Shasha Li, Tufeng Chen, Yuqi Zhou, Zulin Dou, Mengyin Cai, Xiaoyue Zhang, Yanming Chen, Guojun Shi
Summary: This study investigates the role of endoplasmic reticulum stress in mediating obesity-induced diaphragmatic dysfunction. The results show that people with obesity exhibit weakened diaphragmatic strength and lipid accumulation, which is also observed in obese mice. Inhibition of PERK/JNK signaling reverses lipid-induced impairment and elastic damage in C2C12 myotubes.
Article
Multidisciplinary Sciences
Atsushi Yukimoto, Takao Watanabe, Kotaro Sunago, Yoshiko Nakamura, Takaaki Tanaka, Yohei Koizumi, Osamu Yoshida, Yoshio Tokumoto, Masashi Hirooka, Masanori Abe, Yoichi Hiasa
Summary: The study uncovers the close relationship between PERK and RMRP in HCC, with downregulation of RMRP inducing apoptotic cell death. This suggests RMRP could be a potential new therapeutic target for regulating HCC in patients with chronic liver diseases associated with ER stress.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Huizhi Fei, Pu Xiang, Wen Luo, Xiaodan Tan, Chao Gu, Maozhu Liu, Mengyuan Chen, Qiong Wang, Junqing Yang
Summary: This study found that CTRP1 protects against cerebral ischemia reperfusion injury by reducing apoptosis and inhibiting the PERK signaling pathway, suggesting its crucial role in the pathogenesis of CIRI.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Garrett Dalton Smedley, Keenan E. Walker, Shauna H. Yuan
Summary: Neurodegenerative diseases are a growing concern for the aging population, and errors within the PERK pathway have been linked to a variety of pathologies. However, conflicting narratives exist due to the wide array of methodological approaches in genetic and clinical studies. As PERK is connected to pathology, it has become a valuable target for research in understanding and potentially treating neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Haiping Ke, Kevin P. Guay, Terence R. Flotte, Lila M. Gierasch, Anne Gershenson, Daniel N. Hebert
Summary: This study analyzed the production efficiency of α1-antitrypsin (AAT) in Chinese hamster ovary cells and myoblasts, and compared it to liver hepatocytes. The study found that AAT secretion and maturation were most efficient in hepatocytes, while myoblasts had the lowest expression efficiency. Treatment with a specific drug significantly enhanced the secretion of active AAT in myoblasts. These findings may have implications for enhancing the efficacy of gene therapy approaches for AAT and the production of proteins from mRNA vaccines.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Jia-Huang Chen, Chia-Hsien Wu, Chih-Kang Chiang
Summary: ER stress is a trigger for the development of many kidney diseases, and unfolded protein responses (UPRs) play a role in restoring protein homeostasis under this stress. Modulating UPRs and ER proteostasis may have therapeutic potential for kidney diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Environmental
Xudan Liu, Yao Chen, Huanhuan Wang, Yuting Wei, Ye Yuan, Qianqian Zhou, Fang Fang, Sainan Shi, Xiaojing Jiang, Yinqiao Dong, Xin Li
Summary: Arsenic is the primary toxicant among hazardous environmental chemicals, implicated in neurotoxicity such as cognitive dysfunction, neurodevelopmental changes, and neurodegenerative diseases. It is believed that sustained pro-inflammatory response may trigger arsenic-induced neurotoxicity, potentially involving microglia activation and release of pro-inflammatory cytokines. Further research is needed to clarify the role of these cytokines in arsenic-induced neurotoxicity.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Jinlong Tan, Yinju Liu, Fan Yang, Guohua Chen, Yongxiang Fang, Xiaobing He, Zhongzi Lou, Huaijie Jia, Zhizhong Jing, Weike Li
Summary: This study demonstrates that infection with lumpy skin disease virus (LSDV) causes endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). It also shows that an unbalanced ER environment hampers LSDV replication and that PERK-eIF2a and IRE1-XBP1 signaling cascades contribute to LSDV replication.
Article
Environmental Sciences
Wanzhen Wang, Jiafu Guan, Yueying Feng, Shanji Liu, Yu Zhao, Yuanyuan Xu, Hengyi Xu, Fen Fu
Summary: This study investigated the effects of microplastics exposure on ovarian apoptosis in juveniles, revealing that microplastics exposure led to oxidative and endoplasmic reticulum stresses and damage to ovarian function. These findings provide new insights into the potential health risks of children exposed to microplastics.
Article
Environmental Sciences
Xiaoyu Wang, Yu Zhuang, Yukun Fang, Huabin Cao, Caiying Zhang, Chenghong Xing, Xiaoquan Guo, Guyue Li, Ping Liu, Guoliang Hu, Fan Yang
Summary: Excessive copper can trigger ER stress and apoptosis in duck renal tubular epithelial cells via the PERK/ATF4/CHOP signaling pathway. Treatment with PERK inhibitor can ameliorate the adverse effects caused by copper exposure.
ENVIRONMENTAL POLLUTION
(2021)
Article
Biochemistry & Molecular Biology
Vincenzo Vestuto, Giuseppina Amodio, Giacomo Pepe, Manuela Giovanna Basilicata, Raffaella Belvedere, Enza Napolitano, Daniela Guarnieri, Valentina Pagliara, Simona Paladino, Manuela Rodriquez, Alessia Bertamino, Pietro Campiglia, Paolo Remondelli, Ornella Moltedo
Summary: This study demonstrates the neuroprotective effects of cocoa extract and its purified fractions in a cellular model of Parkinson's disease. The cocoa extract targets the PERK sensor, showing significant antioxidant and antiapoptotic activities. Additionally, cocoa inhibits the accumulation of alpha-synuclein in the cells.
Review
Biochemistry & Molecular Biology
Adalberto Merighi, Laura Lossi
Summary: In addition to protein processing, the endoplasmic reticulum (ER) also plays roles in lipid synthesis, molecular transfers, and Ca2+ homeostasis. Proper protein folding and modification in the ER require molecular chaperones and a favorable environment. Disruption in ER conditions or chaperone capacity can lead to the unfolded protein response (UPR), triggering autophagy and potentially causing cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Lin Chen, Ling Pan, Yuexi Zeng, Xiaonan Zhu, Li You
Summary: This study identifies CPNE1 as an important modifier in sarcopenia, which regulates myogenic cell proliferation and differentiation through the PERK-eIF2 alpha pathway. Overexpression of CPNE1 leads to increased muscle atrophy characteristics and reduced muscle fibrosis regeneration and exercise capacity. These findings provide a novel target for the treatment of age-related sarcopenia.
CELL AND TISSUE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Kyle S. Cole, Julia M. D. Grandjean, Kenny Chen, Collin H. Witt, Johanna O'Day, Matthew D. Shoulders, R. Luke Wiseman, Eranthie Weerapana
Article
Cell Biology
Justine Lebeau, Jaclyn M. Saunders, Vivian W. R. Moraes, Aparajita Madhavan, Nicole Madrazo, Mary C. Anthony, R. Luke Wiseman
Article
Multidisciplinary Sciences
Erik A. Blackwood, Khalid Azizi, Donna J. Thuerauf, Ryan J. Paxman, Lars Plate, Jeffery W. Kelly, R. Luke Wiseman, Christopher C. Glembotski
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Julia M. D. Grandjean, Lars Plate, Richard I. Morimoto, Michael J. Bollong, Evan T. Powers, R. Luke Wiseman
ACS CHEMICAL BIOLOGY
(2019)
Editorial Material
Biochemistry & Molecular Biology
R. Luke Wiseman
Article
Cell Biology
Amado Carreras-Sureda, Fabian Jana, Hery Urra, Sylvere Durand, David E. Mortenson, Alfredo Sagredo, Galdo Bustos, Younis Hazari, Eva Ramos-Fernandez, Maria L. Sassano, Philippe Pihan, Alexander R. van Vliet, Matias Gonzalez-Quiroz, Angie K. Torres, Cheril Tapia-Rojas, Martijn Kerkhofs, Ruben Vicente, Randal J. Kaufman, Nibaldo C. Inestrosa, Christian Gonzalez-Billault, R. Luke Wiseman, Patrizia Agostinis, Geert Bultynck, Felipe A. Court, Guido Kroemer, J. Cesar Cardenas, Claudio Hetz
NATURE CELL BIOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Christopher C. Glembotski, Jessica D. Rosarda, R. Luke Wiseman
TRENDS IN MOLECULAR MEDICINE
(2019)
Article
Biochemistry & Molecular Biology
Cristina Puchades, Bojian Ding, Albert Song, R. Luke Wiseman, Gabriel C. Lander, Steven E. Glynn
Correction
Cell Biology
Amado Carreras-Sureda, Fabian Jana, Hery Urra, Sylvere Durand, David E. Mortenson, Alfredo Sagredo, Galdo Bustos, Younis Hazari, Eva Ramos-Fernandez, Maria L. Sassano, Philippe Pihan, Alexander R. van Vliet, Matias Gonzalez-Quiroz, Angie K. Torres, Cheril Tapia-Rojas, Martijn Kerkhofs, Ruben Vicente, Randal J. Kaufman, Nibaldo C. Inestrosa, Christian Gonzalez-Billault, R. Luke Wiseman, Patrizia Agostinis, Geert Bultynck, Felipe A. Court, Guido Kroemer, J. Cesar Cardenas, Claudio Hetz
NATURE CELL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Oktay Kirak, Eugene Ke, Kevin Y. Yang, Anna Schwarz, Lars Plate, Amy Nham, Justin R. Abadejos, Anna Valencia, R. Luke Wiseman, Kathy O. Lui, Manching Ku
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Lara Ibrahim, Jaleh Mesgarzadeh, Ian Xu, Evan T. Powers, R. Luke Wiseman, Michael J. Bollong
Article
Cell Biology
Jaleh S. Mesgarzadeh, Isabelle C. Romine, Ethan M. Smith-Cohen, Julia M. D. Grandjean, Jeffery W. Kelly, Joseph C. Genereux, R. Luke Wiseman
Summary: This study identified ER proteostasis factors involved in ATF6-dependent reductions in destabilized TTR secretion through a mass-spectrometry-based interactomics approach. Activation of ATF6 reduces the secretion and subsequent aggregation of amyloidogenic TTR through increased interactions with ATF6-regulated ER proteostasis factors including BiP and PDIA4. PDIA4 retains destabilized TTR in the ER through a redox-independent mechanism. These findings provide a mechanistic basis for the therapeutic targeting of ATF6 activation to improve treatments for TTR-related amyloid diseases.
Article
Medicine, Research & Experimental
Eun-Jin Lee, Wei-Chieh Jerry Chiang, Heike Kroeger, Chloe Xiaoke Bi, Daniel L. Chao, Dorota Skowronska-Krawczyk, Rebecca R. Mastey, Stephen H. Tsang, Leon Chea, Kyle Kim, Scott R. Lambert, Julia Grandjean, Britta Baumann, Isabelle Audo, Susanne Kohl, Anthony T. Moore, R. Luke Wiseman, Joseph Carroll, Jonathan H. Lin
Article
Biochemistry & Molecular Biology
Lars Plate, Bibiana Rius, Bianca Nguyen, Joseph C. Genereux, Jeffery W. Kelly, R. Luke Wiseman
CELL CHEMICAL BIOLOGY
(2019)