scholarly journals Selective Targeting of the KRAS Codon 12 Mutation Sequence by Pyrrole-Imidazole Polyamideseco-CBI Conjugates

2015 ◽  
Vol 21 (42) ◽  
pp. 14996-15003 ◽  
Author(s):  
Rhys D. Taylor ◽  
Anandhakumar Chandran ◽  
Gengo Kashiwazaki ◽  
Kaori Hashiya ◽  
Toshikazu Bando ◽  
...  
Keyword(s):  
Selective Targeting ◽  
Kras Codon ◽  
Mutation Sequence

scholarly journals Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kiran Todkar ◽  
Lilia Chikhi ◽  
Véronique Desjardins ◽  
Firas El-Mortada ◽  
Geneviève Pépin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Mitochondrial Content ◽  
Sorting Nexin ◽  
Inflammatory Conditions ◽  
Selective Targeting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Insight Into

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.

scholarly journals Inhibition of KRAS codon 12 mutants using a novel DNA-alkylating pyrrole–imidazole polyamide conjugate

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Kiriko Hiraoka ◽  
Takahiro Inoue ◽  
Rhys Dylan Taylor ◽  
Takayoshi Watanabe ◽  
Nobuko Koshikawa ◽  
...  
Keyword(s):  
Kras Codon
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