Transcription coactivator Eya2 is a critical regulator of physiological hypertrophy

► Eya2 directly regulates the expression of mTOR during physiological hypertrophy. ► Eya2 and Six1 synergistically up-regulate mTOR expression. ► Eya2 TG exhibits characteristics of physiological cardiac hypertrophy. ► Mitochondrial integrity is preserved in Eya2 TG hearts under pressure overload. ► Activation of Eya2 and Six1 transcriptional complex is cardioprotective.