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ContributorsRizvi, Hasan (Author) / Hyatt, JP (Thesis director) / Kingsbury, Jeffrey (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor)
Created2023-05
Description

Our current understanding of the mitochondrial genome was revolutionized in 2015 with the discovery of short open reading frames (sORFs) that produced protein products called mitochondrial-derived peptides (MDPs). Interestingly, unlike other proteins produced by the organelle, these MDPs are not directly involved in the electron transport chain but rather serve

Our current understanding of the mitochondrial genome was revolutionized in 2015 with the discovery of short open reading frames (sORFs) that produced protein products called mitochondrial-derived peptides (MDPs). Interestingly, unlike other proteins produced by the organelle, these MDPs are not directly involved in the electron transport chain but rather serve the role of metabolic regulators. In particular, one of these peptides called MOTS-c has been shown to regulate glucose and fat metabolism in an AMPK-dependent manner. With its capacity to enter the mitochondria and impact gene expression, MOTS-c has also displayed the ability to increase aerobic exercise performance by triggering elevated synthesis of the HO-1 antioxidant. Overall these findings position MOTS-c as a promising treatment for metabolic diseases as well as a potential dietary supplement to boost ATP availability.

ContributorsRizvi, Hasan (Author) / Hyatt, JP (Thesis director) / Kingsbury, Jeffrey (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor)
Created2023-05
ContributorsRizvi, Hasan (Author) / Hyatt, JP (Thesis director) / Kingsbury, Jeffrey (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor)
Created2023-05
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Description
A series of mitochondria targeting probes was synthesized for the purpose of exploring the feasibility of a mitochondria targeting fluorescent sensor. Of the probes, the probe with a two carbon spacer showed the best co-localization from staining with the established MitoTracker Red® FM, indicating a potential development of the probe

A series of mitochondria targeting probes was synthesized for the purpose of exploring the feasibility of a mitochondria targeting fluorescent sensor. Of the probes, the probe with a two carbon spacer showed the best co-localization from staining with the established MitoTracker Red® FM, indicating a potential development of the probe into mitochondria targeting sensor. However, cytotoxicity was observed for the probe with a six carbon spacer. Three additional mitochondria targeting fluorescent probes of longer spacer groups were synthesized, but the cytotoxicity was not observed to be as high as that of the probe with a two carbon spacer. The cytotoxicity was characterized to be that of caspase dependent cell death. To screen for a possible effect on apoptosis due to the mitochondrial probe, three fluorescent fusion proteins binding the anti-apoptotic proteins were designed and expressed. Each purified fusion protein was then incubated with the cytotoxic mitochondrial probe, and the mixture was isolated by running an affinity column. The fluorescence analysis of eluted fractions showed preliminary data of possible interaction between the protein and the mitochondrial probe.
ContributorsLee, Fred (Author) / Meldrum, Deirdre R. (Thesis director) / Tian, Yanqing (Committee member) / Zhang, Liqiang (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-12