Yeast revealed to be a versatile organism for studying endocytosis. Here, inhibition of endocytosis by H(2)O(2) and its correlation with apoptotic cell death were ascertained in Saccharomyces cerevisiae. We found that H(2)O(2) causes alterations in vacuolar morphology and a concentration-dependent inhibition of endocytosis. We also found that H(2)O(2)-induced endocytosis inhibition is a reversible process that occurs in the early phase of the apoptotic cascade, preceding chromatin condensation and DNA fragmentation. Additionally, mutants affecting early steps of the endocytic pathway display sensitivity to H(2)O(2). As endocytosis inhibition was also observed with acetic acid, it may be a broader cellular dysfunction of oxidative stress-induced toxicity in yeast.
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http://dx.doi.org/10.1111/j.1567-1364.2012.00825.x | DOI Listing |
Mol Biol Rep
January 2025
Department of Biology, Adelphi University, One South Avenue, P.O. Box 701, Garden City, NY, 11530-0701, USA.
Background: von Hippel-Lindau (VHL) hereditary cancer syndrome is caused by mutations in the VHL tumor suppressor gene and is characterized by a predisposition to form various types of tumors, including renal cell carcinomas, hemangioblastomas, and pheochromocytomas. The protein products of the VHL gene, pVHL, are part of an ubiquitin ligase complex that tags hypoxia inducible factor alpha (HIF-α) for proteosomal degradation. pVHL has also been reported to bind to atypical protein kinase C (aPKC).
View Article and Find Full Text PDFTalanta
January 2025
State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
Misfolded neurotoxic proteins, such as Tau protein, spread within the brain in many neurodegenerative diseases. Receptors play an important role in the recognition of spreading proteins for endocytosis. Blocking the receptors is essential to inhibit neurotoxic proteins spreading in the brain.
View Article and Find Full Text PDFBiosens Bioelectron
January 2025
Deparment of Pharmacy, the Second Affiliated Hospital, Zhejiang University School of Medicine and College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address:
Antibody-drug conjugates (ADC) have emerged as an important class of therapeutic agents that combine the target specificity of a monoclonal antibody with the potency of a cytotoxic payload. Despite clinical success, our understanding of receptor endocytosis and ADC toxicity remains limited. Less than 1% of ADCs reach tumors, raising concerns about off-target cytotoxicity.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.
View Article and Find Full Text PDFPlant Physiol
January 2025
State Key Laboratory of Microbial Metabolism & Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China, P. R.
Mitochondria have generated the bulk of ATP to fuel cellular activities, including membrane trafficking, since the beginning of eukaryogenesis. How inhibition of mitochondrial energy production will affect the form and function of the endomembrane system and whether such changes are specific in today's cells remain unclear. Here, we treated Arabidopsis thaliana with antimycin A (AA), a potent inhibitor of the mitochondrial electron transport chain (mETC), as well as other mETC inhibitors and an uncoupler.
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