Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response.
Cell
; 166(6): 1539-1552.e16, 2016 Sep 08.
Article
em En
| MEDLINE
| ID: mdl-27610574
ABSTRACT
Defects in mitochondrial metabolism have been increasingly linked with age-onset protein-misfolding diseases such as Alzheimer's, Parkinson's, and Huntington's. In response to protein-folding stress, compartment-specific unfolded protein responses (UPRs) within the ER, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood. We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small-molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resposta ao Choque Térmico
/
Citosol
/
Resposta a Proteínas não Dobradas
/
Lipídeos
/
Mitocôndrias
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos