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IMPACT OF PROTEIN LSO22/CCDC124 ON RIBOSOMES DURING CELLULAR STRESS

- Divya Krishnakumar

 

Ribosomes are cellular organelles consisting of a complex made of proteins and ribonucleic acid (RNA) in almost equal amounts. They were first observed by the biologist George Emil Palade as dense granules under an electron microscope.



CELLULAR OXIDATIVE STRESS

The cells of our body produce reactive molecules called free radicals during normal metabolic processes that are carried out within the body. These unstable free radicals bond with neighboring atoms in order to fill their outer atomic shell completely, and become stable. These free radicals carry the potential to damage the cells in its proximity by reacting with cellular molecules, and hence to control the damage thus caused, our cells produce molecules known as antioxidants, which donate their electrons to the free radicals, so that the outer shell of the free radicals can be completed whilst keeping the essential molecules of the cell intact.





When there is an imbalance of free radicals and antioxidants, leading to an accumulation of free radicals in the body, it leads to a condition known as oxidative stress, where the antioxidants formed by our cells are not able to combat the effects of the radicals, which can cause damage to our deoxyribonucleic acid (DNA) or to other important structures in the cell.


Under certain circumstances, some antioxidants get converted to pro-oxidants, which function in a way similar to free radicals, that is, they take electrons from other molecules. This also contributes to chemical instability that leads to oxidative stress. Free radicals are formed within the body via exposure to radiation (especially ultraviolet radiation), smoking and are also naturally produced within the body during inflammatory reactions.






REACTION OF RIBOSOMES TO OXIDATIVE STRESS


When cells enter a state of oxidative stress, there are several targets that free radicals tend to bond with, such as DNA. These targets are often involved in essential metabolic pathways of the cell, for instance, translation and amino acid synthesis, both of which take place in the ribosomes. One way that free radicals inhibit these processes is by oxidizing the enzymes involved in the processes. This leads to a decrease in the activity of such processes.


Another effect of the oxidation of proteins by free radicals is the loss of the function and structure of such proteins, which leads to the production of further aggregates that are toxic to the cell. Similarly, many macromolecules involved in major metabolic pathways of the cells are often common targets for free radicals. Due to their abundance throughout the cell, RNA, especially ribosomal RNA (rRNA), tends to be a more common target for oxidation by free radicals than DNA. When ribosomes are subjected to oxidative stress, oxidised 23S rRNA inhibits the ribosome from functioning optimally during protein synthesis. The oxidation of various nitrogenous bases within the nucleic acid leads to various outcomes, with detrimental effects to protein synthesis observed at different sites of the ribosomal elongation cycle.






IMPORTANCE OF PROTEIN LSO22/CCDC124


The protein Lso2/CCDC124 was recently found to be vital to ribosomal function, despite being only 92 amino acids long, which is small enough to escape the eyes of even experienced scientists studying cell biology.


As discovered by a Yale University research team headed by Wendy Gilbert, professor of molecular biophysics and biochemistry, the absence of protein Lso2/CCDC124 in yeast caused disruption in the function of ribosomes in cases of cellular stress.


According to Gilbert, the protein is vital in some conditions, but not as much in other conditions. Lso2/CCDC124 is conserved across all species, but its surplus in people suffering from liver cancer has been linked to decreased survival time. The disturbance in the functioning of cellular machinery due to improper ribosome functioning can lead to adverse prognosis of cancer.

 

For more, visit - https://www.ncbi.nlm.nih.gov/pubmed/10693912


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