Intracellular lipid surveillance by small G protein geranylgeranylation.
Nature
; 605(7911): 736-740, 2022 05.
Article
in En
| MEDLINE
| ID: mdl-35585236
ABSTRACT
Imbalances in lipid homeostasis can have deleterious effects on health1,2. Yet how cells sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption remains unclear. Here we describe a mechanism for intracellular lipid surveillance in Caenorhabditis elegans that involves transcriptional inactivation of the nuclear hormone receptor NHR-49 through its cytosolic sequestration to endocytic vesicles via geranylgeranyl conjugation to the small G protein RAB-11.1. Defective de novo isoprenoid synthesis caused by lipid depletion limits RAB-11.1 geranylgeranylation, which promotes nuclear translocation of NHR-49 and activation of rab-11.2 transcription to enhance transporter residency at the plasma membrane. Thus, we identify a critical lipid sensed by the cell, its conjugated G protein, and the nuclear receptor whose dynamic interactions enable cells to sense metabolic demand due to lipid depletion and respond by increasing nutrient absorption and lipid metabolism.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monomeric GTP-Binding Proteins
/
Caenorhabditis elegans Proteins
Type of study:
Screening_studies
Limits:
Animals
Language:
En
Journal:
Nature
Year:
2022
Document type:
Article
Affiliation country:
United States