Date of Award
Spring 5-5-2025
Document Type
Thesis
Degree Name
Bachelor of Arts
Department
Biochemistry & Molecular Biology
First Advisor
Peter Kropp
Abstract
Recessive mutations to the gene MECR lead to Mitochondrial Enoyl-CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome, a rare mitochondrial disease. MECR is part of the mitochondrial fatty acid synthesis II (mtFASII) pathway, reducing the last step of the pathway to produce acyl chains of varying lengths that include precursors of essential cofactors for proteins in most stages of cellular respiration. Deletion of mecr-1, the Caenorhabditis elegans MECR ortholog, significantly shortens lifespan, leads to smaller germlines, and produces germline defects that result in near complete sterility. Contrary to our predictions, the transition zone—the area where undifferentiated germ cells transition from mitosis to meiosis—of mutant worms was smaller than wild type (WT). Germ cell proliferation rates were also decreased, although proliferation unexpectedly occurred in the primary spermatocytes. While the mechanism of germline dysfunction is unclear, we predict RNA binding proteins (RBPs, e.g. GLD-1/LIN-41) involved in the development of germ cells are impaired as our findings are phenotypically similar to RBP mutants. In addition to investigating the germline defects of mecr-1, we have also investigated its C. elegans paralog, mecr-2, whose function is unknown. We hypothesized that mecr-2 would not be necessary, which we tested with lifespan and brood size assays and western blot analysis of lipoic acid (LA) production, the canonical mtFASII product. We found no significant difference between the lifespans or brood sizes of mecr-2 knockout worms and WT, indicating that mecr-2 is not necessary in the presence of mecr-1. However, mecr-1 and mecr-2 mutant strains presented unexpected patterns in LA production, including the retention of LA despite impairment of mtFAS which is the only known pathway through which LA is produced. The observed LA production suggests that there is an unknown mechanism of LA production in C. elegans. In all, we found that mecr-1 mutants have severe germline defects while mecr-2 mutants do not appear to be impaired.
Recommended Citation
Spilsbury, Katherine, "Determining the role and necessity of mecr in Caenorhabditis elegans" (2025). Honors Theses. 987.
https://digital.kenyon.edu/honorstheses/987
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