How long can a person go without sleep? Sleep deprivation is associated with many impaired body functions, and sleep is required to clear toxins from the brain.

Genetic screens in fruit flies have been used to identify genes regulating many basic cellular and physiological processes, including sleep. A recent study by researchers at the University of Pennsylvania and Howard Hughes Medical Institute found that some sleep genes are involved in managing cellular waste in neurons, a process known as autophagy (or self-eating). Non-functional proteins and other cellular debris are loaded into compartments called autophagosomes to be eventually broken down and reused by the cell. The proteins responsible for this process are known as the autophagosomal proteins.

The study, published in online journal eLife, monitored autophagy in a mutant fruit fly mutant (named argus) that sleeps less than others. They followed the autophagosomes in these flies by tagging them with fluorescent proteins, and found more autophagosomes accumulating in the mutants' neurons. This accumulation means that cellular waste is not being cleared efficiently. 

A different mutation in another known autophagy gene, called blue cheese, reduced this autophagosome accumulation. While in argus mutants, autophagosomes do not proceed towards degradation, blue cheese mutants produced fewer autophagosomes to begin with. Interestingly, when neurons don't express blue cheese or other autophagy genes, fruit flies sleep more.  

The question remained, does sleep itself also affect the autophagy pathway?

The authors found normal adult flies had more autophagosomes in the early night than in the early morning. Mechanical sleep deprivation of the flies also lead to such an autophagosomal accumulation in neurons. To rule out the possibility of an indirect effect, the authors used a sleep-inducing drug on the flies. They saw that this reduced autophagosome accumulation, emphasizing the relation between sleep and autophagy.

Scientists are closer to a molecular picture of sleep, with a direct link between sleep and a cellular housekeeping pathway. But it's still unclear how this pathway translates into a physiological response. More work in this direction could help researchers find suitable drugs to treat sleep disorders.