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Electronic Thesis and Dissertation Repository

Theses/Dissertations

2019

Mitochondria

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Phenotypic And Metabolic Plasticity In Canine Cellular Reprogramming, Ian C. Tobias May 2019

Phenotypic And Metabolic Plasticity In Canine Cellular Reprogramming, Ian C. Tobias

Electronic Thesis and Dissertation Repository

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) derived from large mammals reproduce few characteristics displayed by rodent or human counterparts. This is complicated by the inherent plasticity of mammalian ESC/iPSC cultures that resemble a variety of developmental stages including the naïve and primed pluripotent states. Defining the extrinsic signals that modulate the developmental identity of canine ESC/iPSC (i.e. primed versus naïve) will improve knowledge integration with more sophisticated rodent and primate research. In this thesis, I sought to determine if manipulation of the culture environment can promote nuclear and metabolic reprogramming of canine cell lines towards a …


Structure And Function Of Stomatin-Like Protein 2, Safee Mian Apr 2019

Structure And Function Of Stomatin-Like Protein 2, Safee Mian

Electronic Thesis and Dissertation Repository

Stomatin-like protein 2 (SLP-2), a member of the SPFH superfamily, is a mitochondrial inner membrane protein required for optimal mitochondrial respiration. SLP-2 binds to the important mitochondrial phospholipid cardiolipin (CL) and has been proposed to mediate formation of CL-enriched microdomains that would foster respiratory chain supercomplex (RCS) formation and stability. However, little is known about how SLP-2 structure facilitates its cellular function. The goal of this thesis was to elucidate if and how SLP-2 oligomerizes and by what means does it bind CL.

Biophysical analysis of the expressed SLP-2 SPFH domain, either with or without flanking residues, indicates it to …


Alpha-Synuclein Toxicity Is Caused By Mitochondrial Dysfunction, Michael G. Tauro Feb 2019

Alpha-Synuclein Toxicity Is Caused By Mitochondrial Dysfunction, Michael G. Tauro

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting roughly 1% of the population over the age of sixty years. Alpha-synuclein (aSyn) is a protein implicated in both familial and idiopathic forms of PD, yet despite the wealth of data implicating aSyn as a causative agent in PD, the mechanisms underlying its toxicity remain mostly unknown. Mitochondrial dysfunction is a major hallmark of PD, yet there is only limited evidence linking aSyn toxicity to mitochondrial dysfunction. My study establishes a novel aSyn model in respiring yeast cells, which allows me to explore how aSyn affects mitochondrial homeostasis and …