Faculty Sponsor(s)
Megan Bestwick
Location
Jereld R. Nicholson Library: Grand Avenue
Subject Area
Biochemistry and Molecular Biology
Description
Mitochondria are traditionally known for their essential roles in cellular metabolism and energy production. In humans, approximately 80 protein subunits make up the oxidative phosphorylation (OXPHOS) pathway in the mitochondrial inner membrane, 13 of which are encoded by the mitochondrial DNA (mtDNA) and the remaining encoded by the nuclear genome. The mtDNA is circular molecule present in multiple copies per mitochondrion, and the two strands of human mtDNA are categorized as the heavy strand and light strand. The light strand has one promoter region (LSP), while the heavy strand has two (HSP1 and HSP2). These promoter regions are essential for the transcription of the 13 proteins encoded by mtDNA that are essential for the OXPHOS pathway. Mutations in mtDNA have been known to cause diseases and disorders, some of which can arise from mutations in the non-coding promoter regions. We generated known point mutations in the promoter regions of mtDNA with the aim to observe the effects on mitochondrial transcription in vitro. The point mutations we selected are at the 195 and 309 base pair locations upstream of the LSP. The T196C mutation is associated with bipolar disorder, and the C309CC mutation is weakly associated with Alzheimer's disease. Our work utilizes an in vitro recombinant human mitochondrial transcription assay to assess changes in mitochondrial transcription with these mutations compared to wild type. Understanding mitochondrial transcriptional changes in the presence of these mutations potentially gives insight into underlying contributions to these neurological disorders.
Recommended Citation
Hedberg, Madeline and Bestwick, Megan, ": Mitochondrial DNA disease mutations effect on in vitro transcription" (2022). Linfield University Student Symposium: A Celebration of Scholarship and Creative Achievement. Event. Submission 6.
https://digitalcommons.linfield.edu/symposium/2022/all/6
: Mitochondrial DNA disease mutations effect on in vitro transcription
Jereld R. Nicholson Library: Grand Avenue
Mitochondria are traditionally known for their essential roles in cellular metabolism and energy production. In humans, approximately 80 protein subunits make up the oxidative phosphorylation (OXPHOS) pathway in the mitochondrial inner membrane, 13 of which are encoded by the mitochondrial DNA (mtDNA) and the remaining encoded by the nuclear genome. The mtDNA is circular molecule present in multiple copies per mitochondrion, and the two strands of human mtDNA are categorized as the heavy strand and light strand. The light strand has one promoter region (LSP), while the heavy strand has two (HSP1 and HSP2). These promoter regions are essential for the transcription of the 13 proteins encoded by mtDNA that are essential for the OXPHOS pathway. Mutations in mtDNA have been known to cause diseases and disorders, some of which can arise from mutations in the non-coding promoter regions. We generated known point mutations in the promoter regions of mtDNA with the aim to observe the effects on mitochondrial transcription in vitro. The point mutations we selected are at the 195 and 309 base pair locations upstream of the LSP. The T196C mutation is associated with bipolar disorder, and the C309CC mutation is weakly associated with Alzheimer's disease. Our work utilizes an in vitro recombinant human mitochondrial transcription assay to assess changes in mitochondrial transcription with these mutations compared to wild type. Understanding mitochondrial transcriptional changes in the presence of these mutations potentially gives insight into underlying contributions to these neurological disorders.
