자료유형  

 학위논문

Control Number  

0016933483

International Standard Book Number  

9798379728090

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Sung, Andrew Y.

Publication, Distribution, etc. (Imprint  

[S.l.] : The University of Wisconsin - Madison., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(129 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

General Note  

Advisor: Keck, James L.;Pagliarini, David J.

Dissertation Note  

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Mitochondria are the powerhouse of the cell. At the core of this function is the oxidative phosphorylation (OxPhos) system. OxPhos is carried out by five protein complexes, of which complex I (CI) is the largest and serves a pivotal role as the primary gateway for electrons into the OxPhos system. While the structure and function of the CI holoenzyme have been characterized extensively at molecular resolution, the molecular details of the process by which this multimeric complex is assembled remains unclear. In recent years, many key advances in our understanding of CI assembly have been made using a systems biochemistry approach. These advances are detailed in chapter 1 of this dissertation, as well as a general overview of systems biochemistry and other examples of its use in mitochondrial biology.In chapter 2, I describe a systematic mutational analysis for deepening our understanding of CI assembly. By measuring the functional consequence of each single-amino-acid-substitution in the CI assembly factor NDUFAF6, we are able glean insights into its molecular function, identify a strategy to bypass its dysfunction, and provide a resource to help diagnose NDUFAF6-related disease. In chapter 3, I explore the regulation of mitochondrial gene expression in OxPhos assembly using an integrated proteomic and transcriptomic dataset. I also use this dataset to examine the regulation of genes involved in coenzyme Q biosynthesis. Chapter 4 summarizes the major findings of chapter 2-3 and outlines next steps for each project. Altogether, this dissertation illustrates the systems biochemistry approach: starting with systematic, large-scale experiments, generating mechanistic hypotheses, and testing them through targeted biochemistry.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Cellular biology.

Index Term-Uncontrolled  

Complex I

Index Term-Uncontrolled  

Deep mutational scanning

Index Term-Uncontrolled  

Mitochondria

Index Term-Uncontrolled  

Respiratory chain

Index Term-Uncontrolled  

Systems biochemistry

Added Entry-Corporate Name  

The University of Wisconsin - Madison Cellular and Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 84-12B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:639931