V-ATPase/TORC1-mediated ATFS-1 translation directs mitochondrial UPR activation in C. elegans.
J Cell Biol
; 222(1)2023 01 02.
Article
em En
| MEDLINE
| ID: mdl-36314986
ABSTRACT
To adapt mitochondrial function to the ever-changing intra- and extracellular environment, multiple mitochondrial stress response (MSR) pathways, including the mitochondrial unfolded protein response (UPRmt), have evolved. However, how the mitochondrial stress signal is sensed and relayed to UPRmt transcription factors, such as ATFS-1 in Caenorhabditis elegans, remains largely unknown. Here, we show that a panel of vacuolar H+-ATPase (v-ATPase) subunits and the target of rapamycin complex 1 (TORC1) activity are essential for the cytosolic relay of mitochondrial stress to ATFS-1 and for the induction of the UPRmt. Mechanistically, mitochondrial stress stimulates v-ATPase/Rheb-dependent TORC1 activation, subsequently promoting ATFS-1 translation. Increased translation of ATFS-1 upon mitochondrial stress furthermore relies on a set of ribosomal components but is independent of GCN-2/PEK-1 signaling. Finally, the v-ATPase and ribosomal subunits are required for mitochondrial surveillance and mitochondrial stress-induced longevity. These results reveal a v-ATPase-TORC1-ATFS-1 signaling pathway that links mitochondrial stress to the UPRmt through intimate crosstalks between multiple organelles.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
ATPases Vacuolares Próton-Translocadoras
/
Proteínas de Caenorhabditis elegans
/
Resposta a Proteínas não Dobradas
/
Alvo Mecanístico do Complexo 1 de Rapamicina
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Suíça