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Regulation of the Mitochondrial Pyruvate Carrier by the Wnt/beta-catenin pathway

Semester: Summer 2023

Presentation description

Metabolism is one of the most tightly regulated cellular processes important for the maintenance of homeostasis. The mitochondrial pyruvate carrier (MPC) is a transmembrane protein that resides in the inner mitochondria membrane and facilitates the entry of pyruvate, which is necessary in several metabolic reactions such as TCA cycle. Our lab has previously shown that MPC expression is negatively correlated with Wnt/beta-catenin target genes; however, the molecular mechanism behind the regulation of the MPC by the Wnt/beta-catenin signaling pathway is not known. Based on our preliminary observations, we hypothesize that beta-catenin acts as a repressor of the MPC. To investigate this regulation, we first performed a Fluorescence-activated cell sorting (FACS)-based genetic screening assay in liver cancer cells and found that beta-catenin acts as a genetic repressor of the MPC. Furthermore, we treated liver cancer cells for 48h with GSK3 inhibitors (CHIR99021 or LY2090314) to activate the Wnt/beta-catenin pathway, and MPC protein was analyzed by western blot. Interestingly, we found that MPC protein was reduced in cells treated with CHIR99021 or LY2090314 when compared to untreated cells. To investigate whether MPC expression was affected at the transcriptional level, we performed RT-qPCR and found that MPC1 transcripts were decreased in liver cancer cells treated with CHIR99021 or LY2090314. Overall, our results suggest that activation of beta-catenin results in decreased MPC transcripts and protein levels. Taken together, we proposed a model where beta-catenin acts as a repressor of the MPC in liver cancer cells. Future studies will be focus on characterizing the mechanism by which MPC expression is regulated by the Wnt/beta-catenin pathway and the significance of this regulation in cell metabolism and cell fate.

Presenter Name: Nimo Abdi

Presentation Type: Poster
Presentation Format: In Person
Presentation #51
College: Medicine
School / Department: Biochemistry
Research Mentor: Luis Cedeno-Rosario
Date | Time: Thursday, Aug 3rd | 10:30 AM