Carbon Dioxide Regulates Cholesterol Levels Through SREBP2

Overview

Journal PLoS Biol

Specialty Biology

Date 2023 Nov 15

PMID 37967106

Authors

Nityanand Bolshette

Saar Ezagouri

Vaishnavi Dandavate

Iuliia Karavaeva

Marina Golik

Hu Wang

Peter J Espenshade

Timothy F Osborne

Xianlin Han

Gad Asher

Affiliations

Soon will be listed here.

Abstract

In mammals, O2 and CO2 levels are tightly regulated and are altered under various pathological conditions. While the molecular mechanisms that participate in O2 sensing are well characterized, little is known regarding the signaling pathways that participate in CO2 signaling and adaptation. Here, we show that CO2 levels control a distinct cellular transcriptional response that differs from mere pH changes. Unexpectedly, we discovered that CO2 regulates the expression of cholesterogenic genes in a SREBP2-dependent manner and modulates cellular cholesterol accumulation. Molecular dissection of the underlying mechanism suggests that CO2 triggers SREBP2 activation through changes in endoplasmic reticulum (ER) membrane cholesterol levels. Collectively, we propose that SREBP2 participates in CO2 signaling and that cellular cholesterol levels can be modulated by CO2 through SREBP2.

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