Autophagy Governs Circadian Clock
Autophagy Governs Circadian Clock
Our brains’ circadian clocks control key physiological processes—sleep, body temperature, organ function and maintaining blood glucose levels. Disruption of the clock can lead to diabetes and other metabolic diseases. In a mouse study published in June in Cell Metabolism, Rajat Singh, M.D., M.B.B.S., and colleagues discovered that autophagy—the cellular process for cleaning up and recycling old proteins and other material—helps regulate circadian rhythms and also governs the daily fluctuations in blood glucose levels.
The researchers found that autophagic digestion also selectively targets proteins controlling the circadian clock, most notably the clock protein CRY1. CRY1 is a key regulator of circadian cycles and also helps maintain blood glucose levels by inhibiting the liver from forming and secreting glucose.
The researchers found that by digesting CRY1 mainly between 3 p.m. and 11 p.m., autophagy encourages the liver’s output of glucose during those hours—the period when mice are not feeding and therefore need a boost in blood glucose to fuel their activities. Feeding the mice a high-fat diet accelerated CRY1 degradation via autophagy, which contributed to obesity-associated hyperglycemia. Conversely, blocking CRY1 degradation led to a decrease in blood glucose levels.
Dr. Singh is an associate professor of medicine and of molecular pharmacology at Einstein.
