Article
Cell Biology
Michal Eisenberg-Bord, Naama Zung, Javier Collado, Layla Drwesh, Emma J. Fenech, Amir Fadel, Nili Dezorella, Yury S. Bykov, Doron Rapaport, Ruben Fernandez-Busnadiego, Maya Schuldiner
Summary: Mitochondrial functions are tightly regulated by nuclear activity, and communication between these organelles is facilitated by contact sites. In yeast, specific areas of contact between the nucleus and mitochondria were identified, with the uncharacterized protein Ybr063c (Cnm1) playing a role as a molecular tether on the nuclear membrane. Cnm1 mediates contact by interacting with Tom70 on mitochondria and is regulated by phosphatidylcholine, linking phospholipid homeostasis with contact extent.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Gunes Parlakgul, Ana Paula Arruda, Song Pang, Erika Cagampan, Nina Min, Ekin Guney, Grace Yankun Lee, Karen Inouye, Harald F. Hess, C. Shan Xu, Gokhan S. Hotamisligil
Summary: This study reveals the complex structural organization of organelles in liver tissue and highlights the significant alterations in obese mice. The functional importance of these structural changes on cellular and systemic metabolism is also demonstrated.
Article
Biochemical Research Methods
Nan Wu, Mingdong Yao, Wenhai Xiao, Tianyu Dong, Haidi Ma, Yingjin Yuan, Xianli Du, Ying Wang
Summary: The current study proposes a modular compartmentalization strategy for identifying and modifying the bottleneck step in agroclavine overproduction. The agroclavine synthetic pathway was reconstituted in yeast to enhance pathway efficiency and improve agroclavine yield.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Phuong Thi Mai Nguyen, Yuki Ishiwata-Kimata, Yukio Kimata
Summary: The unfolded protein response (UPR) is a cellular response to deal with the accumulation of unfolded proteins in the endoplasmic reticulum (ER). This study demonstrates that constitutive induction of UPR in nonstress conditions leads to growth retardation, which can be partially rescued by weak ER stress. Additionally, the stable expression of ER-localized GFP in UPR-induced cells enhances UPR activity and promotes the production of triglycerides and heterogenous carotenoids. These findings have implications for metabolic engineering and the production of valuable lipidic molecules.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Agricultural Engineering
Xiang Xiu, Yi Sun, Yaokang Wu, Ke Jin, Lisha Qu, Yanfeng Liu, Jianghua Li, Guocheng Du, Xueqin Lv, Long Liu
Summary: This study achieved highly efficient 7-DHC synthesis by remodeling the complicated sterol synthesis modules. By overexpressing multiple genes and a transcription factor mutant, as well as applying CRISPR-mediated activation and repression systems, the titer of 7-DHC was successfully increased. Furthermore, by compartmentalizing enzymes and enlarging the endoplasmic reticulum lumen, the titer of 7-DHC was further enhanced, reaching the highest reported level so far.
BIORESOURCE TECHNOLOGY
(2022)
Article
Biology
Tianyao Xiao, Viplendra P. S. Shakya, Adam L. Hughes
Summary: Deficiencies in mitochondrial import result in the toxic accumulation of non-imported precursor proteins, with some being redirected to the endoplasmic reticulum (ER). The ER delivery of endogenous mitochondrial trans-membrane proteins, particularly from the SLC25A family, is dependent on the GET complex. Loss of the GET pathway poses detrimental effects on yeast cells experiencing mitochondrial import failure.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemical Research Methods
Yiting Shi, Tianyu Dong, Boxuan Zeng, Mingdong Yao, Ying Wang, Zexiong Xie, Wenhai Xiao, Yingjin Yuan
Summary: This study successfully manipulated the production of parthenolide, a sesquiterpene lactone and precursor for the anti-glioblastoma drug ACT001, in microorganisms through a comprehensive strategy involving P450 source screening, NADPH supply, and endoplasmic reticulum size rewiring. The highest titers of parthenolide and costunolide achieved in microbes were 31.0 mg/L and 648.5 mg/L, respectively, demonstrating the potential for sustainable production of sesquiterpene lactones and highlighting a general strategy for manipulating multiple plant-derived P450s in microbes.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Ana Cristina Jaramillo-Madrid, Elia Lacchini, Alain Goossens
Summary: This article discusses the recent advances in synthetic biology for increasing the performance of terpene pathways in plants and yeasts. Through engineering of organelles such as the endoplasmic reticulum and peroxisome, as well as the use of specialized transporters, synthetic biology offers solutions for efficient and sustainable production of high-value terpenes, addressing the shortcomings of extraction from natural resources.
CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY
(2022)
Article
Cell Biology
Rasha Khaddaj, Jiri Stribny, Stephanie Cottier, Roger Schneiter
Summary: Lipid droplets (LDs) form and associate closely with the endoplasmic reticulum (ER) to store energy-rich lipids. Membrane-anchored perilipins induce expansion and vesiculation of the perinuclear membrane, forming crescent-shaped membrane domains with LD-like properties. These domains are enriched in diacylglycerol (DAG) and ER proteins important for LD biogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Endocrinology & Metabolism
Ming Yang, Chongbin Liu, Na Jiang, Yan Liu, Shilu Luo, Chenrui Li, Hao Zhao, Yachun Han, Wei Chen, Li Li, Li Xiao, Lin Sun
Summary: The endoplasmic reticulum (ER) is an active organelle involved in various physiological processes. Recent studies have shown that dysfunction of the ER plays a role in the progression of kidney disease, particularly diabetic nephropathy (DN). This review discusses the function of the ER, the regulation of homeostasis through the unfolded protein response (UPR) and ER-phagy, as well as the impact of abnormal ER homeostasis in renal cells in DN. Additionally, potential therapeutic targets for DN related to maintaining ER homeostasis are also explored.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Herong Wang, Guozhen Jiang, Nan Liang, Tianyu Dong, Mengying Shan, Mingdong Yao, Ying Wang, Wenhai Xiao, Yingjin Yuan
Summary: 8-Hydroxygeraniol, an important component of insect sex pheromones and defensive secretions, can be produced sustainably and efficiently using microbial production. This study successfully increased the production of 8-hydroxygeraniol in Saccharomyces cerevisiae by implementing an integrated strategy consisting of G8H and CPR compatibility, ER engineering, and NADPH supply. The highest-reported titer of more than 1.0 g/L 8-hydroxygeraniol in S. cerevisiae was achieved in a 5.0 L fed-batch fermentation. This work not only provides a sustainable way for de novo biosynthesis of 8-hydroxygeraniol but also contributes to P450 engineering in microbes.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anna Kowalczuk, Krzysztof Marycz, Justyna Kornicka, Sylwia Groborz, Justyna Meissner, Malwina Mularczyk
Summary: In this study, the protective effects of THCV isolated from Cannabis sativa L. against ER stress in adipose-derived mesenchymal stem cells were evaluated. It was found that THCV can prevent subcellular alterations, restore cell functions upon ER stress, and decrease the expression of genes involved in the UPR pathway. These findings suggest that THCV has potential as a therapeutic compound for metabolic diseases associated with ER stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Huong Thi Phuong, Yuki Ishiwata-Kimata, Yukio Kimata
Summary: Upon ER stress, cells initiate the unfolded protein response (UPR) through Ire1. This study investigates how the accumulation of misfolded transmembrane proteins in the ER induces UPR. The authors find that GFP-tagged Ire1 co-localizes with aggregated Pma1-2308-mCherry on the ER membrane. A specific point mutation in Ire1 impairs its activation upon lipid bilayer stress (LBS), compromising the co-localization and UPR induced by Pma1-2308-mCherry. The study suggests that Pma1-2308-mCherry affects the properties of the ER membrane at aggregation sites, leading to Ire1 recruitment, self-association, and activation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Daria Sicari, Federica G. Centonze, Raphael Pineau, Pierre-Jean Le Reste, Luc Negroni, Sophie Chat, M. Aiman Mohtar, Daniel Thomas, Reynald Gillet, Ted Hupp, Eric Chevet, Aeid Igbaria
Summary: This study identified the accumulation of ER luminal proteins in the cytosol of glioblastoma cells, and demonstrated that ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. The study also showed that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53, suggesting a mechanism named ER to Cytosol Signaling (ERCYS) which provides a selective advantage to tumor cells through gain-of-cytosolic functions.
Review
Biochemistry & Molecular Biology
Keisuke Mochida, Hitoshi Nakatogawa
Summary: Autophagy is a degradation system in eukaryotic cells that controls the mass and functions of organelles by degrading excess or defective portions. The endoplasmic reticulum (ER) is an organelle with specific functions that dynamically changes its mass and shape to maintain or regulate its functions. Elaborate mechanisms are required for the proper degradation of the ER.