mTORC1 inhibition impairs activation of the unfolded protein response and induces cell death during ER stress in cardiomyocytes
Year: 2023
Type: article
Abstract: Cells coordinate translation rates with protein quality control to ensure that protein synthesis is initiated primarily when proper protein folding can be achieved. Long-term activity of the unfolded protein response is therefore associated with an inhibition of mTORC1, a central regulator of protein synthesis. Here, we found that mTORC1 is transiently activated early in response to ER stress before it is inhibited. Importantly, partial mTORC1 activity remained essential for the upregulation of adaptive unfolded protein response genes and cell survival in response to ER stress. Our data reveal a complex regulation of mTORC1 during ER stress and its involvement in the adaptive unfolded protein response.
Authors: Christoph Hofmann, Zoe Löwenthal, Marjan Aghajani, Randal J. Kaufman, Hugo A. Katus, Norbert Frey, Christopher C. Glembotski, Mirko Völkers, Shirin Doroudgar
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4379981660