Document Type

Honors Thesis

Abstract

Mitohormesis is the biological concept that a mild dose of mitochondrial stress has beneficial effects on an organism, leading to increased longevity. While mitohormesis has been demonstrated to result in a conserved increase in lifespan across multiple species, the molecular players involved in this phenomenon still need to be fully identified. Here, we investigated the role of KGB-1, the C. elegans homolog of mammalian c-Jun N-terminal kinase (JNK) in the regulation of mitohormesis. Specifically, what substrate(s) interact downstream of the stress-activated kinase KGB-1 to mediate mitohormesis? Primary methodology was lifespan analysis using C. elegans in which each predicted KGB-1 interactor gene’s function was reduced by RNA interference (RNAi). For each RNAi strain, lifespan of C. elegans was monitored and used to construct survival graphs. Results indicated that the effect of KGB-1 on mitohormesis longevity was dependent on the specific substrate that was knocked down. Of the KGB-1 substrates that were reduced following RNAi, the GTPase NOG-1 that is required for ribosome assembly showed the greatest effect. Our preliminary results suggest a novel mechanism of mitohormesis by the regulation of ribosome assembly through the interaction of KGB-1 and NOG-1. Biochemical assays will be carried out to further study this in mammalian cells.

Publication Date

5-1-2018

Language

English

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