TOMM40 RNA Transcription in Alzheimer’s Disease Brain and Its Implication in Mitochondrial Dysfunction
| Autor: | Lesley Leong, Eun Gyung Lee, Chang En Yu, Jessica Tulloch, Sunny Chen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mitochondrial DNA Pseudogene pseudogene RNA QH426-470 Mitochondrion Biology Primary transcript Article TOMM40 gene Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Transcription (biology) mitochondrial dysfunction Genetics Human genome Alzheimer’s disease Gene RNA transcription 030217 neurology & neurosurgery Genetics (clinical) |
| Zdroj: | Genes Volume 12 Issue 6 Genes, Vol 12, Iss 871, p 871 (2021) |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes12060871 |
| Popis: | Increasing evidence suggests that the Translocase of Outer Mitochondria Membrane 40 (TOMM40) gene may contribute to the risk of Alzheimer’s disease (AD). Currently, there is no consensus as to whether TOMM40 expression is up- or down-regulated in AD brains, hindering a clear interpretation of TOMM40’s role in this disease. The aim of this study was to determine if TOMM40 RNA levels differ between AD and control brains. We applied RT-qPCR to study TOMM40 transcription in human postmortem brain (PMB) and assessed associations of these RNA levels with genetic variants in APOE and TOMM40. We also compared TOMM40 RNA levels with mitochondrial functions in human cell lines. Initially, we found that the human genome carries multiple TOMM40 pseudogenes capable of producing highly homologous RNAs that can obscure precise TOMM40 RNA measurements. To circumvent this obstacle, we developed a novel RNA expression assay targeting the primary transcript of TOMM40. Using this assay, we showed that TOMM40 RNA was upregulated in AD PMB. Additionally, elevated TOMM40 RNA levels were associated with decreases in mitochondrial DNA copy number and mitochondrial membrane potential in oxidative stress-challenged cells. Overall, differential transcription of TOMM40 RNA in the brain is associated with AD and could be an indicator of mitochondrial dysfunction. |
| Databáze: | OpenAIRE |
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