Retrotransposon activation by distressed mitochondria in neurons.

Retrotransposon activation by distressed mitochondria in neurons. Biochem Biophys Res Commun. 2020 Feb 27;: Authors: Baeken MW, Moosmann B, Hajieva P Abstract Retrotransposon activation occurs in a variety of neurological disorders including multiple sclerosis and Alzheimer's Disease. While the origins of disease-related retrotransposon activation have remained mostly unidentified, this phenomenon may well contribute to disease progression by inducing inflammation, disrupting transcription and, potentially, genomic insertion. Here, we report that the inhibition of mitochondrial respiratory chain complex I by pharmacological agents widely used to model Parkinson's disease leads to a significant increase in expression of the ORF1 protein of the long interspersed nucleotide element 1 (LINE1) retrotransposon in human dopaminergic LUHMES cells. These findings were recapitulated in midbrain lysates from accordingly treated wild-type mice that mimic Parkinson's disease. Retrotransposon activation was paralleled by a loss of DNA cytosine methylation, providing a potential mechanism of retrotransposon mobilization. Loss of DNA methylation as well as retrotransposon activation were suppressed by the mitochondrial antioxidant phenothiazine, indicating that the well-established production of oxidants by inhibited complex I was causing these effects. Retrotransposon activation in some brain disorders may be less of a primary disease trigger rathe...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research