Researcher(s)
- Emily Fowler, Biological Sciences, University of Delaware
Faculty Mentor(s)
- Jessica Tanis, Biological Sciences, University of Delaware
Abstract
Elevated plasma level of the amino acid homocysteine (Hcy) is a risk factor for multiple age-related conditions, including cognitive decline, neurodegenerative disorders, cardiovascular disease, and low skeletal muscle mass. In one-carbon metabolism, Hcy can be converted to methionine by methionine synthase, with B12 as an essential cofactor. Hcy can also be converted to cystathionine by cystathionine beta-synthase (CBS) in the first step of the transsulfuration pathway. Mutations in CBS or vitamin B12 deficiency can lead to the buildup of Hcy in the blood, resulting in altered phospholipid abundance. The Tanis lab knocked out cbs-1, the C. elegans homolog for human CBS. Loss of cbs-1 causes elevated levels of Hcy and a decline in muscle function. Additionally cbs-1 mutants exhibit structural defects in the mitochondria, which are restored with B12 and choline supplementation. My goal this summer was to observe how loss of C. elegans cbs-1 as well as dietary supplementation with vitamin B12 and choline affects mitochondrial stress in the model organism C. elegans. I used cbs-1 mutant and control worms expressing hsp-6 promoter::GFP, a reporter measuring the mitochondria unfolded protein response, to show mitochondrial stress. I imaged the worms using a fluorescent microscopy and measured fluorescence intensity between the wildtype and mutant animals raised on the different diets. The more fluorescence the worms have the more mitochondrial stress the worm exhibits. I predict that the cbs-1 mutant will have increased mitochondrial stress, that is restored by B12 and choline supplementation because of the previous data regarding the structural defects in the mitochondria.