Autophagy gets a brake: DAP1, a novel mTOR substrate, is activated to suppress the autophagic process

Itay Koren, Eran Reem, Adi Kimchi

Research output: Contribution to journalComment/debate

31 Scopus citations


Autophagy, a highly regulated catabolic process, is controlled by the action of positive and negative regulators. While many of the positive mediators of autophagy have been identified, very little is known about negative regulators that might counterbalance the process. We recently identified death-associated protein 1 (DAP1) as a suppressor of autophagy and as a novel direct substrate of mammalian target of rapamycin (mTOR). We found that DAP1 is functionally silent in cells growing under rich nutrient supplies through mTOR-dependent inhibitory phosphorylation on two sites, which were mapped to Ser3 and Ser51. During amino acid starvation, mTOR activity is turned off resulting in a rapid reduction in the phosphorylation of DAP1. This caused the conversion of the protein into a suppressor of autophagy, thus providing a buffering mechanism that counterbalances the autophagic flux and prevents its overactivation under conditions of nutrient deprivation. Based on these studies we propose the "gas and brake" concept in which mTOR, the main sensor that regulates autophagy in response to amino acid deprivation, also controls the activity of a specific balancing brake to prevent the overactivation of autophagy.

Original languageEnglish
Pages (from-to)1179-1180
Number of pages2
Issue number8
StatePublished - 16 Nov 2010
Externally publishedYes


  • Amino acid starvation
  • Autophagy
  • DAP1
  • Phosphorylation
  • mTOR


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