Mitochondrial TRAP1 regulates the unfolded protein response in the endoplasmic reticulum.
Neurochem Int
; 58(8): 880-7, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21338643
ABSTRACT
Stress in mitochondria or the endoplasmic reticulum (ER) independently causes cell death. Recently, it was reported that ER stress causes mitochondrial dysfunction via p53-upregulated modulator of apoptosis (PUMA). However, little is known regarding the mitochondria molecules that mediate ER dysfunction. The present study revealed that tumor necrosis factor receptor-associated protein 1 (TRAP1), which localizes in the mitochondria, is associated with the unfolded protein response (UPR) in the ER. TRAP1 knockdown activated the ER-resident caspase-4, which is activated by ER stress, to induce cell death in humans. However, TRAP1 knockdown cells did not show a significant increase in the level of cell death at least within 24 h after early phase of ER stress in comparison with that of the control cells. This finding could be attributed to a number of reasons. TRAP1 knockdown failed to activate caspase-9, which is activated by activated caspase-4. In addition, TRAP1 knockdown increased the basal level of GRP78/BiP expression, which protects cells, and decreased the basal level of C/EBP homologous protein (CHOP) expression, which induces cell death, even under ER stress. Thus, the present study revealed that mitochondria could be a potential regulator of the UPR in the ER through mitochondrial TRAP1.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Choque Térmico HSP90
/
Proteínas Mitocondriais
/
Retículo Endoplasmático
/
Resposta a Proteínas não Dobradas
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article