ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1.

ABSTRACT: Inhibition of the master growth regulator mTORC1 (mechanistic target of rapamycin complex 1) slows ageing across phyla, in part by reducing protein synthesis. Various stresses globally suppress protein synthesis through the integrated stress response (ISR), resulting in preferential translation of the transcription factor ATF-4. Here we show in C. elegans that inhibition of translation or mTORC1 increases ATF-4 expression, and that ATF-4 mediates longevity under these conditions independently of ISR signalling. ATF-4 promotes longevity by activating canonical anti-ageing mechanisms, but also by elevating expression of the transsulfuration enzyme CTH-2 to increase hydrogen sulfide (H₂S) production. This H₂S boost increases protein persulfidation, a protective modificat

SUBMITTER: Statzer C 

PROVIDER: S-EPMC8857226 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature