Review
Biochemistry & Molecular Biology
John C. Christianson, Pedro Carvalho
Summary: This article discusses recent advances in understanding the mechanisms of ERAD and its impact on the regulation of ER functions.
Article
Cell Biology
Maria Livia Sassano, Alexander R. R. van Vliet, Ellen Vervoort, Sofie Van Eygen, Chris van den Haute, Benjamin Pavie, Joris Roels, Johannes V. V. Swinnen, Marco Spinazzi, Leen Moens, Kristina Casteels, Isabelle Meyts, Paolo Pinton, Saverio Marchi, Leila Rochin, Francesca Giordano, Blanca Felipe-Abrio, Patrizia Agostinis
Summary: ER-mitochondria appositions play a critical role in the transfer of ions and phospholipids between these organelles and impact mitochondrial bioenergetics. However, the molecular mechanisms involved in this process are not well understood. This study reveals that PERK acts as an adaptor to recruit the lipid transfer protein E-Syt1 at ER-mitochondria contact sites, enabling lipid transport and maintaining mitochondrial homeostasis. These findings provide insights into the molecular components and functions of the lipid trafficking machinery at ER-mitochondria contact sites.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kohta Miura, Riko Katsuki, Shusei Yoshida, Ren Ohta, Taku Tamura
Summary: ERAD is an essential process for maintaining cell function and preventing ER stress. EDEM1 was found to be involved in accelerating the degradation of EGFR via ERAD, highlighting its physiological role in maintaining specific target proteins and providing a potential approach to regulate the expression of clinically important proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Plant Sciences
Sofia Reyes-Impellizzeri, Adrian A. Moreno
Summary: This review focuses on the impact of alterations in components of ERQC, ERAD, and UPR on plant responses to abiotic stresses. Evidence shows a clear connection between ERAD and UPR mechanisms, but the connection of ERQC components with these processes or their possible client proteins is lacking. Proteomics approaches are suggested to uncover the identity of these proteins and their connection to ER proteostasis.
FRONTIERS IN PLANT SCIENCE
(2021)
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.
Article
Cell Biology
Keisuke Mochida, Toshifumi Otani, Yuto Katsumata, Hiromi Kirisako, Chika Kakuta, Tetsuya Kotani, Hitoshi Nakatogawa
Summary: In this study, the researchers uncovered the mechanism of action of the nucleophagy receptor Atg39 in the formation of NDVs. Atg39 is anchored to the outer nuclear membrane via its transmembrane domain and is also associated with the inner nuclear membrane through membrane-binding amphipathic helices, linking these membranes together. Additionally, the aggregation of Atg39 causes the nuclear envelope to protrude and pinch off to generate NDVs.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Environmental Sciences
Xiaoyu Wang, Fan Yang, Xiaomin Tian, Haihua Huo, Xinrun Li, Haitong Wu, Jianying Guo
Summary: Excessive copper can cause histopathological damage to duck cerebrums, disrupt the balance of trace elements, induce oxidative stress and activation of ER quality control, resulting in duck cerebrums damage.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Nicola A. Scott, Laura J. Sharpe, Andrew J. Brown
Summary: MARCHF6 is a large multi-pass E3 ubiquitin ligase embedded in the membranes of the endoplasmic reticulum, participating in endoplasmic reticulum associated degradation and being regulated by cholesterol. It plays a role in cell metabolism and its regulation, substrates, and role in human health and disease are still not fully understood.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Ola Jassar, Murad Ghanim
Summary: The carrot psyllid in Israel transmits CLso haplotype D in a persistent manner, causing significant economic losses. This study confirms the role of the endoplasmic reticulum (ER) in inducing immune responses and programmed cell death upon CLso infection in the insect gut.
INSECT MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Mari A. Piirainen, Alexander D. Frey
Summary: Yeasts are widely used for biopharmaceutical production, but N-glycosylated biopharmaceuticals manufactured with yeasts are missing on the market. N-linked glycans play crucial roles in protein properties and folding, but current glycoengineering approaches face challenges.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kei Taguchi, Masayuki Kaneko, Serika Motoike, Kana Harada, Izumi Hide, Shigeru Tanaka, Norio Sakai
Summary: The ubiquitin E3 ligase HRD1 is demonstrated to be involved in the degradation of SERT protein, promoting SERT ubiquitination and affecting its uptake activity. This involvement in endoplasmic reticulum-associated degradation contributes to the membrane trafficking and functional regulation of SERT.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Satarupa Bhaduri, Analine Aguayo, Yusuke Ohno, Marco Proietto, Jasmine Jung, Isabel Wang, Rachel Kandel, Narinderbir Singh, Ikran Ibrahim, Amit Fulzele, Eric J. Bennett, Akio Kihara, Sonya E. Neal
Summary: This study reveals the association between the pseudoprotease Dfm1 and the SPOTS complex, highlighting their roles in sphingolipid metabolism. Additionally, Dfm1 is found to play a crucial role in the ER export and degradation of Orm2. These findings provide insights into the molecular mechanisms underlying sphingolipid metabolism and its implications in disease.
Article
Biochemistry & Molecular Biology
Kei Miyano, Shuichiro Okamoto, Mizuho Kajikawa, Takuya Kiyohara, Chikage Kawai, Akira Yamauchi, Futoshi Kuribayashi
Summary: This study characterized missense mutations in p22(phoX) (L51Q, L52P, E53V, and P55R) that enhance the degradation of the protein in the endoplasmic reticulum (ER) and its binding to Derlin-1, a component of ER-associated degradation (ERAD). These mutations contribute to chronic granulomatous disease (CGD). The oxidation of Cys-50 appears to regulate the degradation of p22(phoX) and its interaction with Derlin-1.
Article
Biochemistry & Molecular Biology
Jowita Nowakowska-Golacka, Justyna Czapiewska, Hanna Sominka, Natalia Sowa-Rogozinska, Monika Slominska-Wojewodzka
Summary: EDEM1 is an important regulatory factor involved in APP metabolism, as it recognizes misfolded APP proteins and directs them to cytosol for degradation, leading to decreased secretion of Aβ.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nga H. Nguyen, Jeffrey L. Brodsky
Summary: Potassium channels are essential for physiological processes and disruptions in their quality control can lead to human diseases. This article summarizes the mechanisms underlying potassium channel quality control, highlights diseases associated with channel misfolding, and suggests potential therapeutic routes.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Review
Parasitology
Nicholas C. Smith, Cibelly Goulart, Jenni A. Hayward, Andreas Kupz, Catherine M. Miller, Giel G. van Dooren
Summary: Toxoplasmosis, a disease caused by a parasitic infection, poses various threats to both humans and animals. Controlling toxoplasmosis involves education, sanitation measures, therapeutic treatments, preventive options, and vaccine development.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yi Tong Vincent Aw, Azadeh Seidi, Jenni A. Hayward, Jiwon Lee, F. Victor Makota, Melanie Rug, Giel G. van Dooren
Summary: Fe-S clusters are essential for the survival of eukaryotes, with independent biosynthesis pathways occurring in different compartments of the cell. Little is known about cytosolic Fe-S cluster biosynthesis in apicomplexan parasites, but it has been found that NBP35 in Toxoplasma gondii localizes to the outer mitochondrial membrane and is critical for parasite proliferation.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Jenni A. Hayward, Esther Rajendran, Soraya M. Zwahlen, Pierre Faou, Giel G. van Dooren
Summary: The protein composition of Complex III in apicomplexan parasites differs from that of mammalian hosts, with novel or highly divergent components identified in this study. One specific subunit, TgQCR11, was found to be critical for parasite proliferation and mitochondrial activity. This research provides important insights into the unique features of Complex III in apicomplexans and its evolution in eukaryotes.
Article
Multidisciplinary Sciences
Joy M. Zeng, Sanduni V. Hapuarachchi, Sarah H. Shafik, Rowena E. Martin, Kiaran Kirk, Giel G. van Dooren, Adele M. Lehane
Summary: This study found that all three FNT proteins of T. gondii are located on the cell membrane, with TgFNT1 making the largest contribution to l-lactate transport during the parasite lytic cycle. Genetic analysis showed that these three genes can be disrupted individually or together without affecting the parasite's proliferation cycle.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Stephen J. Fairweather, Esther Rajendran, Martin Blume, Kiran Javed, Birte Steinhofel, Malcolm J. McConville, Kiaran Kirk, Stefan Broer, Giel G. van Dooren
Summary: The study demonstrates that apicomplexan parasites can scavenge lysine and arginine through the TgApiAT6-1 protein, which plays a key role in the disease-causing stage of Toxoplasma gondii and is essential for parasite proliferation. The uptake of cationic amino acids by TgApiAT6-1 is regulated by various factors, highlighting the complex mechanisms involved in essential amino acid absorption by these intracellular parasites.
Article
Biochemistry & Molecular Biology
Elizabeth D. English, Amandine Guerin, Jayesh Tandel, Boris Striepen
Summary: Cryptosporidium is a significant cause of diarrhea around the world, affecting children's mortality and nutrition. The parasite's life cycle unfolds in less than 3 days in a single host, without the need for environmental stimuli. This study investigates the cell division of asexual and sexual stage parasites and establishes a life cycle model that contradicts the traditional coccidian life cycle.
Review
Parasitology
Andrew E. Maclean, Jenni A. Hayward, Diego Huet, Giel G. van Dooren, Lilach Sheiner
Summary: The mitochondrial respiratory chain is crucial for various biological processes in eukaryotes, including respiration. Studies of the respiratory chain in apicomplexan parasites have revealed unique features and highlighted the diversity of mitochondrial form and function across eukaryotic life.
TRENDS IN PARASITOLOGY
(2022)
Article
Multidisciplinary Sciences
Deyun Qiu, Jinxin V. Pei, James E. O. Rosling, Vandana Thathy, Dongdi Li, Yi Xue, John D. Tanner, Jocelyn Sietsma Penington, Yi Tong Vincent Aw, Jessica Yi Han Aw, Guoyue Xu, Abhai K. Tripathi, Nina F. Gnadig, Tomas Yeo, Kate J. Fairhurst, Barbara H. Stokes, James M. Murithi, Krittikorn Kumpornsin, Heath Hasemer, Adelaide S. M. Dennis, Melanie C. Ridgway, Esther K. Schmitt, Judith Straimer, Anthony T. Papenfuss, Marcus C. S. Lee, Ben Corry, Photini Sinnis, David A. Fidock, Giel G. van Dooren, Kiaran Kirk, Adele M. Lehane
Summary: The G358S mutation in PfATP4 decreases the sensitivity of ATP4 to inhibition by cipargamin and (+)-SJ733, thereby protecting parasites from disruption of Na+ regulation.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Ian S. Cohn, Sarah E. Henrickson, Boris Striepen, Christopher A. Hunter
Summary: Cryptosporidium is a common parasite that infects gut cells and causes diarrhea, which can be chronic and life-threatening in individuals with compromised immune function. Certain immune deficiencies are associated with increased risk of severe cryptosporidiosis. Understanding the impact of different immune deficiencies on the risk of Cryptosporidium infection can reveal parasite restriction mechanisms and help identify new strategies to manage this common pathogen.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Microbiology
Amandine Guerin, Katherine M. Strelau, Konstantin Barylyuk, Bethan A. Wallbank, Laurence Berry, Oliver M. Crook, Kathryn S. Lilley, Ross F. Waller, Boris Striepen
Summary: This study reveals the process of how Cryptosporidium invades and remodels intestinal epithelial cells to establish a complex interface structure. By generating a whole-cell spatial proteome and using genetic and cell biological experimentation, the study identifies secreted effector proteins and discovers multiple organelles, including a novel secretory organelle. It also demonstrates that secreted proteins contribute to the assembly of different structures at the parasite-host interface, allowing Cryptosporidium to subjugate its host cell.
CELL HOST & MICROBE
(2023)
Article
Microbiology
Jayesh Tandel, Katelyn A. Walzer, Jessica H. Byerly, Brittain Pinkston, Daniel P. Beiting, Boris Striepen
Summary: The parasite Cryptosporidium infects millions of people worldwide each year, leading to life-threatening diarrheal disease. Infection occurs via ingestion of oocysts and transmission relies on fecal shedding of new oocysts. The transcription factor AP2-F is essential for oocyst shedding and controls the transcription of genes encoding crystalloid body proteins, which are exclusively expressed in female gametes.
Article
Chemistry, Medicinal
William Nguyen, Madeline G. Dans, Iain Currie, Jon Kyle Awalt, Brodie L. Bailey, Chris Lumb, Anna Ngo, Paola Favuzza, Josephine Palandri, Saishyam Ramesh, Jocelyn Penington, Kate E. Jarman, Partha Mukherjee, Arnish Chakraborty, Alexander G. Maier, Giel G. van Dooren, Tony Papenfuss, Sergio Wittlin, Alisje Churchyard, Jake Baum, Elizabeth A. Winzeler, Delphine Baud, Stephen Brand, Paul F. Jackson, Alan F. Cowman, Brad E. Sleebs
Summary: The discovery of a new class of antimalarial compounds, the 7-N-substituted-3-oxadiazole quinolone, was made through screening the Janssen Jumpstarter library. The optimized compound, WJM228, showed potent antimalarial activity with good metabolic stability in vitro. It was found to target the Q(o) site of cytochrome b and exhibited resistance to drug-resistant parasites.
ACS INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Matthew Martinez, Shrawan Kumar Mageswaran, Amandine Guerin, William David Chen, Cameron Parker Thompson, Sabine Chavin, Dominique Soldati-Favre, Boris Striepen, Yi-Wei Chang
Summary: This study visualizes the F-actin architecture in Cryptosporidium parvum and Toxoplasma gondii using cryo-ET, revealing the subcellular origin and path of F-actin during gliding motility. The findings provide important insights into the invasion mechanism of these apicomplexan parasites.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Public, Environmental & Occupational Health
Ian H. Gilbert, Sumiti Vinayak, Boris Striepen, Ujjini H. Manjunatha, Ibrahim A. Khalil, Wesley C. Van Voorhis
Article
Biology
Jenni A. Hayward, Esther Rajendran, F. Victor Makota, Brad J. Bassett, Michael Devoy, Teresa Neeman, GielG van Dooren
Summary: The mitochondrial electron transport chain (ETC) plays critical roles in biological functions and can be targeted by anti-parasitic drugs. This study provides methods to assess ETC function and identify inhibitors in parasites, as well as to locate ETC defects and potential targets.