TY - JOUR
T1 - Carbon dioxide regulates cholesterol levels through SREBP2
AU - Bolshette, Nityanand
AU - Ezagouri, Saar
AU - Dandavate, Vaishnavi
AU - Karavaeva, Iuliia
AU - Golik, Marina
AU - Wang, Hu
AU - Espenshade, Peter J.
AU - Osborne, Timothy F.
AU - Han, Xianlin
AU - Asher, Gad
N1 - Publisher Copyright:
© 2023 Bolshette et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023/11
Y1 - 2023/11
N2 - AU In mammals,: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly 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.
AB - AU In mammals,: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly 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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U2 - 10.1371/journal.pbio.3002367
DO - 10.1371/journal.pbio.3002367
M3 - Article
C2 - 37967106
AN - SCOPUS:85177024033
SN - 1544-9173
VL - 21
JO - PLoS biology
JF - PLoS biology
IS - 11
M1 - e3002367
ER -