Figure 3. Effectors of cardiac circadian clock.

(A) Circadian H₂O₂ release and Prx III redox cycling. During the resting phase, mitochondrial H₂O₂ level is low, Prx III is able to scavenge all the mitochondrial H₂O₂ through catalytic cycle. While in the active phase, the H₂O₂ production is increased due to increased cardiac metabolism, which lead to hyperoxidization of Prx III and the formation of the inactive Prx III-SO₂. Excessive H₂O₂ released into cytosol oxidizes Srx leading to the formation of the Srx:HSP30 complex, which is required to reactivate Prx III.

(B) Circadian regulation of PKA/β-adrenergic and CaN signaling, resulting in low diastolic intracellular Ca²⁺ concentration ([Ca²⁺]_i) in the active phase which favors increased contractility, and high diastolic [Ca²⁺]_I in the resting phase which favors hypertrophy.