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A Chemical Approach to Detect and Characterize The Activities of Mitochondrial ATP-dependent Protease Lon and ClpXP

Sha, Zhou
http://rave.ohiolink.edu/etdc/view?acc_num=case1595239191845497

Abstract Details

2020, Doctor of Philosophy, Case Western Reserve University, Chemistry.
Mitochondria are essential sources of reactive oxygen species (ROS). The amount of ROS increases as human beings getting older and leads to the oxidative damage of mitochondrial proteins, membranes, and nucleic acids, affecting the ATP synthesis ability and metabolic functions, such as tricarboxylic acid cycle, fatty acid oxidation, the urea cycle, etc. Two mammalian ATP-dependent serine proteases, Lon and ClpXP (Caseinolytic Protease complex containing subunits X, the ATPase component and P, the proteolytic component), are both synthesized in the cytoplasm as precursors and then translocated into the mitochondrial matrix where they are processed to be the enzyme complexes. Our lab is interested in understanding the role of human Lon and ClpXP in cell mitochondria integrity maintenance. Since Lon and ClpXP have different substrate cleavage specific sites, our lab has generated substrates and inhibitors for human Lon and ClpXP from their protein cleavage profile. In this project, I reported the characterizations of the human ClpXP specific peptide substrate and inhibitor in vitro. These lab-designed chemical tools have also been tested in human cell lysate to confirm their ability to explicitly monitoring and inhibiting hLon and hClpXP proteolytic activity. I have also used these chemical tools to study the relationship between hClpXP activity and oxidative stress. To summarize the information obtained in this study, I discussed the possibility of these lab-designed chemical tools as active site-directed activity probe (ASAP) agents in cell culture studies.
Irene Lee (Advisor)
133 p.
Chemistry
enzymes; hydrolases; peptides; enzyme kinetic;

Recommended Citations

Citations

  • Sha, Z. (2020). A Chemical Approach to Detect and Characterize The Activities of Mitochondrial ATP-dependent Protease Lon and ClpXP [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1595239191845497

    APA Style (7th edition)

  • Sha, Zhou. A Chemical Approach to Detect and Characterize The Activities of Mitochondrial ATP-dependent Protease Lon and ClpXP. 2020. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1595239191845497.

    MLA Style (8th edition)

  • Sha, Zhou. "A Chemical Approach to Detect and Characterize The Activities of Mitochondrial ATP-dependent Protease Lon and ClpXP." Doctoral dissertation, Case Western Reserve University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1595239191845497

    Chicago Manual of Style (17th edition)

case1595239191845497
48
© 2020, some rights reserved.Creative Commons License A Chemical Approach to Detect and Characterize The Activities of Mitochondrial ATP-dependent Protease Lon and ClpXP by Zhou Sha is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.