Premium
Identification of oxidized mitochondrial mRNA in human neurons under oxidative stress
Author(s) -
Rana Joram,
Kharel Prakash,
Basu Soumitra
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.651.21
Subject(s) - neurodegeneration , mitochondrion , oxidative stress , reactive oxygen species , microbiology and biotechnology , biology , respiratory chain , rna , mitochondrial ros , biochemistry , chemistry , gene , medicine , disease , pathology
Mitochondrial dysfunction and the overproduction of reactive oxygen species (ROS) are key features of many neurological disorders. Electrons leaking from the electron transport chain (ETC) in the mitochondria reduces molecular oxygen to superoxide, which through enzymatic and non‐enzymatic reactions generates ROS. Under normal physiological conditions ROS are used in cellular homeostasis and cell signaling, but during stress conditions, they are often overproduced. ROS are known to damage biomolecules DNA, RNA, proteins, and lipids. RNA damage has received attention in recent years. Studies in our lab demonstrated that the selective oxidative damage to RNA could lead to altered gene expression and differential production of protein, contributing to neurodegeneration in multiple sclerosis (MS). The mitochondria contain its own DNA, which transcribes into RNA and subsequently gets translated into mitochondrial proteins using its unique machinery. Selective mitochondrial RNA oxidation could disrupt this process, damaging the mitochondrial respiratory chain proteins, and eventually causing more mitochondrial dysfunction, contributing towards the progression of neurodegeneration in MS and other neurological disorders. The SH‐SY5Y human neuronal cells were treated with sodium nitroprusside (SNP, NO · / · OH) to induce stress and generate ROS to mimic the diseased condition. By quantitating cellular RNA, we have displayed the differential mRNA expression of a number of genes during oxidative stress, for example, high expression of superoxide dismutase 1 and carbonyl reductase. In this study, we focused on mRNA transcribed specifically inside the mitochondria to examine which sequences are most susceptible to oxidation by ROS. We found that 9 of the 13 mRNAs transcribed by mitochondria are highly oxidized. The oxidation of these mitochondrial mRNAs might lead to complication in protein synthesis and might play a role in mitochondrial dysfunction. Support or Funding Information Division of Research & Sponsored Programs (SURE program), Kent State University Graduate Student Senate, Kent State University to PK. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .