Defining the transcriptional regulation of ATF5 isoforms during mitochondrial stress across multiple cell types

Summer 2018

Hannah Chi : MCB Neurobiology and Ethnic Studies

Mentor: Andrew Dillin

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 Parkinson’s. 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 gene’s three isoforms to uncover the differential roles of each isoform’s 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.

I would like to thank the Rose Hill Foundation for allowing me to spend my summer enriching my scientific pursuit as a student at Berkeley. This summer, because of the funding provided by the Rose Hill Foundation, I learned how to design and tackle experiments as a scientific researcher in biology. I also learned how to cope with failures and developed the skills to reorient my approaches to answering questions when my previous attempts did not work. I hope that in the future, I can continue to participate in research and strive to broaden our knowledge of the minutia of the cellular workings of the human body.