The cellular switch Rev-erbalpha is an important lithium-sensitive part of the body’s daily clock

Lithium treatment leads to rapid degradation of Rev-erbalpha, a key regulator of the circadian clock.

• GSK3beta phosphorylates and stabilizes Rev-erbalpha, influencing circadian rhythm.
• Lithium inhibits GSK3, resulting in decreased levels of Rev-erbalpha.
• The degradation of Rev-erbalpha activates the expression of the clock gene Bmal1.
• A lithium-insensitive form of Rev-erbalpha disrupts the expression of circadian genes.
• Rev-erbalpha protein stability is essential for the proper functioning of the peripheral circadian clock.

Simplified