Date of Award

Spring 5-8-2026

Document Type

Thesis

Degree Name

Bachelor of Arts

Department

Biochemistry & Molecular Biology

First Advisor

Peter Kropp

Abstract

MEPAN (Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration) syndrome is a rare, mitochondrial disease caused by mutations in a gene called MECR (Mitochondrial Enoyl CoA Reductase). MECR encodes the final catalyst for the mtFAS (mitochondrial Fatty Acid Synthesis) pathway necessary for mitochondrial function. Consequently, mtFAS defects lead to diverse physiological symptoms that obscure the precise disease mechanisms underlying MEPAN syndrome. We used the model organism Caenorhabditis elegans, a hermaphroditic nematode, to elucidate the downstream effects of MECR by deleting its C. elegans ortholog, mecr-1. The mutants, mecr-1(av238), are sterile; they have sperm but no oocytes, likely due to defects in gametogenic programming. We first investigated spermatogenesis and used immunofluorescence microscopy to assess the spatiotemporal expression of FOG-3, a pro-spermatogenic protein that inhibits oogenesis. The expression pattern mirrored wild type C. elegans, indicating that spermatogenesis functions properly. To evaluate oogenesis, we used live imaging and examined the expression of LIN-41, OMA-1/2 , VIT-2, and RME-2. LIN-41 was expressed spatially late but abruptly eliminated, while there was an absence of OMA-1/2 and RME-2 expression as well as accumulation of VIT-2 surrounding the gonad. These results showcased that while mecr-1(av238) germ cells are initiating oogenesis, they fail to progress to meiotic maturation and are not receiving the necessary lipids for oocyte growth. RNAi knockdown of sel-10 and skr-1, the central degrading agents of LIN-41, led to prolonged LIN-41 expression, suggesting deletion of mecr-1 impacts components of SCFSEL-10. These findings are promising steps into uncovering the protein network and functions of mecr-1, and by extension MECR, to understand how symptoms of MEPAN syndrome occur.

Rights Statement

All rights reserved. This copy is provided to the Kenyon Community solely for individual academic use. For any other use, please contact the copyright holder for permission.

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