Defining the transcriptional regulation of ATF5 isoforms during mitochondrial stress across multiple cell types
Mitochondria often decline in function as a normal part of aging. However, mitochondrial dysfunction often has severe consequences and has been linked to neurodegenerative diseases, cancer and infection. Understanding the ways in which mitochondria recover when exposed to proteotoxic environments is therefore a crucial element in constructing better novel treatments to mitochondrial related disease such as Parkinsons. The mitochondrial unfolded protein response has been identified as a key stress signaling pathway regulated by the ATFS-1 transcription factor in the Caenorhabditis elegans model organism system. However, relatively little is known about the mammalian analog of this gene, ATF5. I propose to investigate the ATF5 genes three isoforms to uncover the differential roles of each isoforms upstream promoter. I hypothesize that these three promoters are differentially utilized to confer distinct responses under stress, and understanding these different cellular responses will reveal key insights into the mechanism behind mammalian mitochondrial recovery and, in turn, many age-related diseases associated with decline of mitochondrial function.
Message to Sponsor
- Major: MCB Neurobiology and Ethnic Studies
- Sponsor: Rose Hills Independent
- Mentor: Andrew Dillin