Related Experiment Video
Updated: Sep 9, 2025

Analysis of SCAP N-glycosylation and Trafficking in Human Cells
Published on: November 8, 2016
Suppression of SREBP by a transmembrane protein mutated in cardiomyopathy
Yasushi Takemoto1, Manchir Tserendagva1, Motonari Uesugi2
1Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan.
Abstract:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder characterized by the replacement of myocardial tissue with adipose tissue. One of the frequently mutated proteins in ARVC is TMEM43, which encodes a transmembrane protein primarily localized to the endoplasmic reticulum (ER) and nuclear membranes and stabilized by interacting with squalene synthase (SQS). However, its precise role in ARVC pathogenesis remains unclear. The present study demonstrates that TMEM43 suppresses the expression of SQS and other lipogenic proteins by inhibiting sterol regulatory element-binding proteins (SREBPs). Mechanistic analysis revealed that TMEM43 inhibits nuclear SREBP activity by binding to LRPPRC, which serves as a transcriptional coactivator for SREBP in coordination with PGC1β. TMEM43 sequesters LRPPRC to the nuclear membrane, disrupting its coactivator function and inhibiting SREBP activity. Given the role of SREBPs in adipogenesis, our findings highlight TMEM43 as a key regulator of adipocyte versus cardiomyocyte differentiation.
More Related Videos
09:16Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
07:34Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
Related Concept Videos
Cardiomyopathy IV: Restrictive Cardiomyopathy
Regulation of Nuclear Protein Sorting
Cardiomyopathy III: Hypertrophic Cardiomyopathy
Cardiomyopathy I: Introduction and Classification
Regulation of the Unfolded Protein Response
Cardiomyopathy II: Dilated Cardiomyopathy