Together, these data suggest that in Taz-deficient hearts, displaying a similar heart failure phenotype as in stable patients with BTHS [20], activation of the ISR increases glutamate uptake that serves (1) to fuel the Krebs cycle through anaplerosis, (2) to produce other amino acids such as asparagine and proline, and (3) as a driving force to facilitate the uptake of cysteine via the system xCT, which is utilized for the production of glutathione (Fig. 1). Here, TAFAZZIN is linked to heart failure.