Role of mitochondria in apoptosis induced by the 2-5A system and mechanisms involved

Apoptosis : an International Journal on Programmed Cell Death
E Domingo-Gil, Mariano Esteban

Abstract

The 2-5A system (2-5OAS/RNaseL) is composed of the 2',5'oligoadenylate synthetase 1 (2-5OAS1) and 2-5A-dependent RNase (RNaseL), enzymes that play a key role in antiviral defence mechanisms. Activation of the 2-5A system by double stranded RNA (dsRNA) induces degradation of ribosomal RNAs and apoptosis in mammalian cells. To obtain further information into the molecular mechanisms by which RNaseL induces apoptosis, we expressed human RNaseL and 2-5OAS in HeLa cells using recombinant vaccinia viruses as vectors and we analysed in detail different biochemical markers of apoptosis. In this expression virus-cell system the activation of RNaseL, as index of rRNA degradation, is an upstream event of apoptosis induction. RNaseL induces apoptosis in a caspase-dependent manner (caspases 8, 9 and 2). At the beginning of apoptosis RNaseL and 2-5OAS are localized in the mitochondria and cytosol fractions, while at the onset of apoptosis both enzymes are largely in mitochondria. The 2-5A system induces the release of Cytochrome c from mitochondria to cytosol in a caspase dependent manner. The onset of apoptosis elicits the disruption of mitochondrial membrane potential (delta psi m), as well as the generation of reactive oxygen species (ROS...Continue Reading

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Citations

Dec 30, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Elena Domingo-GilMariano Esteban
May 3, 2011·Human Molecular Genetics·Gloria M PalomoJavier Diaz-Nido
Apr 14, 2011·Molekuliarnaia biologiia·S N Shchelkunov
Jun 23, 2011·PLoS Pathogens·Jazmina L G CruzSonia Zuñiga
Sep 24, 2015·Molecular Medicine Reports·Jing-Wei LiYing-Bin Xiao
Aug 12, 2008·Biochemical and Biophysical Research Communications·Iain Scott, Kristi L Norris
Aug 18, 2012·Advances in Virology·Sergei N Shchelkunov
Mar 7, 2015·Experimental & Molecular Medicine·Un Yung ChoiYoung-Joon Kim
Nov 9, 2017·PLoS Genetics·Samantha R OakesChristopher J Ormandy
Feb 24, 2007·Antonie van Leeuwenhoek·Wael N Hozzein, Michael Goodfellow
May 10, 2020·Apoptosis : an International Journal on Programmed Cell Death·Qiang MaYundai Chen
Sep 17, 2020·International Journal of Molecular Sciences·Sara Pérez-LuzJavier Díaz-Nido
Jan 9, 2021·Molecular and Cellular Neurosciences·Jara Moreno-LoriteJavier Díaz-Nido

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