Dissertation/Thesis Abstract

The NEET Proteins and Their Potential Binding Partners: Diabetes, Life, and Death
by Halim, Danny, M.S., University of California, San Diego, 2012, 88; 1512270
Abstract (Summary)

The NEET family recently emerged as an important class of proteins that are involved in multiple pathologies, including mitochondrial integrity, diabetes, and aging-related diseases. Although two family members, MitoNEET and NAF-1, have high structural similarity, studies and literature reports indicate that the two proteins are involved in different pathologies; while MitoNEET is involved in diabetes, NAF-1 is a key protein in mediating both longevity and skeletal muscle disorders in mice. Both MitoNEET and NAF-1 are essential factors in maintaining mitochondrial integrity and major cellular processes, such as autophagy and oxidative capacity.

MitoNEET and NAF-1 constitute a novel family of [2Fe-2S] cluster containing proteins because of their unique coordination geometry, and they are generating high interest due to their unexpected binding of TZD diabetes drugs in a completely distinct fashion from the paradigm established by the TZD/nuclear transcription factor target PPAR-γ in the treatment of Type-II diabetes. While standard TZD drugs that target PPAR-γ can result in a host of undesirable side effects, MitoNEET targeting does not appear to suffer these limitations.

Here, we report our success in tuning the EM of the [2Fe-2S] center of the outer mitochondrial membrane protein MitoNEET over a range of 700 mV, which is the largest EM range engineered in an FeS protein and, importantly, spans the cellular redox range. We have also learned that NAF-1 has multiple in vivo binding partners, identified several potential binding partners, and shown that NAF-1 is likely highly involved in autophagy, apoptosis, and general cellular stability, longevity, and integrity.

Indexing (document details)
Advisor: Jennings, Patricia
Commitee: Cohen, Seth, Opella, Stanley
School: University of California, San Diego
Department: Chemistry
School Location: United States -- California
Source: MAI 50/06M, Masters Abstracts International
Subjects: Biochemistry
Keywords: Mitoneet, Naf-1
Publication Number: 1512270
ISBN: 978-1-267-39369-2
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