Review
Biochemistry & Molecular Biology
Amitha Muraleedharan, Benoit Vanderperre
Summary: Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease, and its prevalence increases with age. The endolysosomal system plays a major role in the pathogenesis of PD, and studying the genes and proteins involved in this system can lead to potential therapeutic interventions.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Navin Gopaldass, Maria Giovanna De Leo, Thibault Courtellemont, Vincent Mercier, Christin Bissig, Aurelien Roux, Andreas Mayer
Summary: Proteins exit from endosomes through retromer-coated tubular carriers, which affects cellular signaling, lysosomal biogenesis, and various diseases. The coat formation requires overcoming membrane tension. In this study, we investigated the dynamics and driving force of this process using yeast retromer, BAR-domain sorting nexins Vps5 and Vps17, and synthetic lipid tubules. The results showed that the coat forms a static tubular structure by bidirectional oligomerization, and high concentrations of sorting nexins constrict the membrane tubes. However, retromer oligomers are needed to drive constriction at lower concentrations.
Review
Biochemistry & Molecular Biology
Mai K. L. Nguyen, Jaimy Jose, Mohamed Wahba, Marc Bernaus-Esque, Andrew J. Hoy, Carlos Enrich, Carles Rentero, Thomas Grewal
Summary: Cancer cells undergo metabolic adaptions to meet their increased bioenergetic needs, including an increased demand for cholesterol. They uptake cholesterol from low-density lipoproteins (LDL) and distribute it from late endosomes/lysosomes (LE/Lys) to other organelles to promote cancer growth and spread. Understanding the regulation of cholesterol transporters and related proteins in LE/Lys is important for developing treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Thibault Courtellemont, Maria Giovanna De Leo, Navin Gopaldass, Andreas Mayer
Summary: Endo-lysosomal compartments exchange proteins through different processes, including fusion, fission, and endosomal transport carriers. The membrane fission events that occur during these processes are not well understood. This study identifies the CROP complex as a factor that plays a role in membrane fission. The CROP complex consists of members from two protein families and enhances the membrane fission activity of a specific protein. Disrupting the CROP complex prevents fragmentation of lysosome-like structures in yeast and impairs cargo export in mammalian endosomes.
Review
Cell Biology
Liriope Toupenet Marchesi, Marion Leblanc, Giovanni Stevanin
Summary: Hereditary spastic paraplegia (HSP) involves the degeneration of motor neurons and is characterized by clinical and genetic heterogeneity, making it challenging to find effective therapies. Several HSP genes/proteins are linked to the endolysosomal and autophagic pathways, suggesting a functional convergence, which may have implications for understanding the pathological mechanisms of HSP.
Article
Pharmacology & Pharmacy
Hitomi Ashikawa, Hinako Mogi, Takuya Honda, Hiroyuki Nakamura, Toshihiko Murayama
Summary: NPC is caused by a loss of function of NPC1 or NPC2 protein, leading to accumulation of free-cholesterol in cells and resulting in cell damage and neurodegenerative disease. Antiepileptic drug primidone may enhance free-cholesterol trafficking in NPC cells, potentially offering a treatment option for NPC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Elisabet Uribe-Carretero, Guadalupe Martinez-Chacon, Sokhna M. S. Yakhine-Diop, Gema Duque-Gonzalez, Mario Rodriguez-Arribas, Eva Alegre-Cortes, Marta Paredes-Barquero, Saray Canales-Cortes, Elisa Pizarro-Estrella, Antonio Cuadrado, Rosa Ana Gonzalez-Polo, Jose M. Fuentes, Mireia Niso-Santano
Summary: KEAP1 is an adaptor protein that plays an important role in regulating protein degradation. Loss of KEAP1 leads to protein oxidative aggregation and defective autophagy. Our study demonstrates that KEAP1 deficiency affects the endosome-lysosomal pathway, resulting in downregulation of cathepsin D and accumulation of autophagosomes.
Article
Biochemistry & Molecular Biology
Ha Pham, Indira Singaram, Jiachen Sun, Arthur Ralko, Madalyn Puckett, Ashutosh Sharma, Alice Vrielink, Wonhwa Cho
Summary: Cholesterol is essential for mammalian cell membranes, but its site-specific functions have been limited by methodological constraints. A new cholesterol depletion system has been developed, allowing for spatial and temporal manipulation of cellular cholesterol levels.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Immunology
Zhenfeng Wang, Jiadi Lv, Pin Yu, Yajin Qu, Yabo Zhou, Li Zhou, Qiangqiang Zhu, Shunshun Li, Jiangping Song, Wei Deng, Ran Gao, Yuying Liu, Jiangning Liu, Wei-Min Tong, Chuan Qin, Bo Huang
Summary: The study demonstrates the potential therapeutic effect of ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) against SARS-CoV-2 infection by changing endosomal pH and promoting viral degradation. In addition to inhibiting the inflammatory response of alveolar macrophages, AO-MPs increase treatment efficacy in a SARS-CoV-2-infected mouse model without side effects, highlighting the potential use of AO-MPs in treating SARS-CoV-2-infected patients and the feasibility of microparticle therapies for combating emerging respiratory viruses in the future.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Cell Biology
Yuan Gao, Juan Xiong, Qing-Zhu Chu, Wei-Ke Ji
Summary: This study reveals that PDZD8 acts as a tether at ER-LE/lys MCSs and its SMP domain has lipid transfer activities. PDZD8 is crucial for LE/lys positioning and neurite outgrowth.
JOURNAL OF CELL SCIENCE
(2022)
Article
Cell Biology
Eva Alegre-Cortes, Alberto Gimenez-Bejarano, Elisabet Uribe-Carretero, Marta Paredes-Barquero, Andre R. A. Marques, Mafalda Lopes-da-Silva, Otilia V. Vieira, Saray Canales-Cortes, Pedro J. Camello, Guadalupe Martinez-Chacon, Ana Aiastui, Roberto Fernandez-Torron, Adolfo Lopez de Munain, Patricia Gomez-Suaga, Mireia Niso-Santano, Rosa A. Gonzalez-Polo, Jose M. Fuentes, Sokhna M. S. Yakhine-Diop
Summary: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. Fibroblasts derived from DM1 patients show increased autophagy flux, enlarged endosomes, and lysosomes. The binding of EGF to EGFR and the internalization of EGFR are delayed in DM1 cells, but EGF-activated EGFR enhances the phosphorylation of AKT and ERK1/2.
Review
Biochemistry & Molecular Biology
Marijn Kuijpers, Domenico Azarnia Tehran, Volker Haucke, Tolga Soykan
Summary: Neurons present special challenges to the autophagy and endolysosomal systems due to their complex morphology and longevity. These systems play crucial roles in degrading defective proteins, maintaining cellular homeostasis, and participating in signaling in neurons, especially in axons.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Mirco Glitscher, David Heiler Martin, Kathrin Woytinek, Benjamin Schmidt, Denna Tabari, Catharina Scholl, Julia C. Stingl, Evelyn Seelow, Mira Choi, Eberhard Hildt
Summary: The study found that HEV infection leads to decreased cellular cholesterol levels and affects lipid concentrations in patients. Modulating intracellular cholesterol content through drug treatment can impact HEV release, with cholesterol playing a crucial role in this process. This highlights the potential of targeting cholesterol metabolism as an antiviral strategy against HEV.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Plant Sciences
Vimi Kshetrimayum, Rameshwari Heisnam, Ojit Singh Keithellakpam, Pullapanthula Radhakrishnanand, Sai Jyothi Akula, Pulok K. Mukherjee, Nanaocha Sharma
Summary: Paris polyphylla Sm. (Melanthiaceae) is an important and vulnerable herb with a wide range of traditional applications. The extract of P. polyphylla (PPE) showed good antioxidant activity and cytotoxicity against HCT-116 colon cancer cells without significant toxicity to normal cells. PPE also exhibited synergistic effects with 5FU and cisplatin in HCT-116 cells. The anticancer activities of PPE were attributed to its steroidal saponins.
Article
Biochemistry & Molecular Biology
Duc Hung Nguyen, Anne-Claire Mitaine-Offer, Tomofumi Miyamoto, Chiaki Tanaka, Pierre-Simon Bellaye, Bertrand Collin, Odile Chambin, Marie-Aleth Lacaille-Dubois
Summary: A phytochemical study of Cordyline fruticosa Fairchild red from Vietnam led to the isolation of fourteen steroidal glycosides, including twelve previously undescribed and two known ones. The structures of these compounds, mainly spirostanol and furostanol glycosides, were elucidated through spectroscopic analysis. The isolated compounds were evaluated for their cytotoxicity against 4T1 cell line derived from a mouse mammary gland tissue.