Energy deficit-independent stress response in the Frataxin-depleted heart: evidence that Integrated Stress Response can predominate over mTORC1 activation

Cesar Vasquez, Monika Patel, Aishwarya Sivaramakrishnan, Carmen Bekeova, Lauren Anderson-Pullinger, Nadan Wang, Hsin-Yao Tang, Erin L Seifert; bioRxiv 2020.06.12.148361; doi:10.1101/2020.06.12.148361 

 The lack of overt cardiac hypertrophy, consistent with lower global protein translation, suggests that ISR predominated over mTORC1 activation. Suppression of a major ATP demanding process could benefit the FXN-depleted heart, at least short term. Thus, the FXN-depleted heart may enter a protective state, not necessarily linked to a major energy deficit. Finally, we propose the model used here as a pre-clinical model of cardiomyopathy in FRDA.