Abstract

Human High Temperature requirement A2 (HtrA2) also known as Omi, is a serine protease located in the mitochondria with an important function in both cell survival and death. My results show the proteolytic activity of Omi/HtrA2 varies under different conditions. I characterized the optimal condition for Omi/HtrA2 protease activity using an in vitro assay system. Additionally, I identified a new allosteric regulation of Omi/HtrA2 through interaction with a specific substrate, the MUL1 protein. MUL1 is a multifunctional E3 ubiquitin ligase anchored in the outer mitochondrial membrane with domains both inside mitochondria and in the cytoplasm. The data shown here strongly supports the hypothesis that Omi/HtrA2 activity is modulated by a number of different mechanisms. Some of these conditions, such as pH or substrate denaturation might reflect the state of mitochondria under stress. It has been known that Omi/HtrA2 is a stress activated protease, but the mechanism of its regulation has not been fully elucidated. Furthermore, the allosteric regulation of Omi/HtrA2 by specific substrates, can be another mechanism that provides a feedback loop to increase the activity of the enzyme. The findings from this project contribute new information on the mechanisms of activation of Omi/HtrA2 protease. They support the hypothesis that mitochondrial stress might be involved in the regulation of Omi/HtrA2 protease.

Thesis Completion

2022

Semester

Spring

Thesis Chair

Zervos, Antonis S.

Degree

Bachelor of Science (B.S.)

College

College of Medicine

Department

Burnett School of Biomedical Science

Degree Program

Biomedical Sciences

Language

English

Access Status

Open Access

Release Date

3-1-2022

Restricted to the UCF community until 3-1-2022; it will then be open access.

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