Similar findings were independently reported for two other cardiomyopathy models (one from conditional knockout (KO) of a Complex IV subunit, COX10 (Ahola et al, 2022), and the other from KO of the cardiolipin remodeling protein Tafazzin (Huynh et al, 2022; Zhu et al, 2022)), together supporting the idea that the DELE1 mt-ISR mediates at least some mitochondria-to-nucleus signaling in response to mitochondrial stress in vivo. The gene discussed is DELE1; the disease is cardiomyopathy.