Spatial colocalization and functional link of purinosomes with mitochondria.
Science
; 351(6274): 733-7, 2016 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-26912862
ABSTRACT
Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria. Moreover, the number of purinosome-containing cells responded to dysregulation of mitochondrial function and metabolism. To explore the role of intracellular signaling, we performed a kinome screen using a label-free assay and found that mechanistic target of rapamycin (mTOR) influenced purinosome assembly. mTOR inhibition reduced purinosome-mitochondria colocalization and suppressed purinosome formation stimulated by mitochondria dysregulation. Collectively, our data suggest an mTOR-mediated link between purinosomes and mitochondria, and a general means by which mTOR regulates nucleotide metabolism by spatiotemporal control over protein association.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Purinas
/
Serina-Treonina Quinases TOR
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2016
Tipo de documento:
Article