The fidelity of translation is crucial in prokaryotes and for the nuclear-encoded proteins of eukaryotes, however little is known about the role of mistranslation in mitochondria and its effects on metabolism. We generated yeast and mouse models with error-prone and hyperaccurate mitochondrial translation fidelity and found that translation rate is more important than translational accuracy for cell function in mammals. We found that mitochondrial mistranslation reduces overall mitochondrial translation and the rate of respiratory complex assembly, however in mammals this is compensated for by increased mitochondrial protein stability and upregulation of the citric acid cycle. Moreover, mitochondrial stress signaling enables the recovery of mitochondrial translation via mitochondrial biogenesis, telomerase expression and cell proliferation, normalizing metabolism. Conversely, we show that increased fidelity of mitochondrial translation reduces the rate of protein synthesis without eliciting the mitochondrial stress response. Consequently, the rate of translation cannot be recovered causing dilated cardiomyopathy. Our findings reveal mammalian specific signaling pathways that can respond to changes in the fidelity of mitochondrial protein synthesis