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PAYWALL > Cell Competition Is Driven by Autophagy

cell competition autophagy cell death jnk hid nfκb

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#1 Engadin

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Posted 10 October 2019 - 05:21 PM


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S O U R C E :   Developmental Cell

 

 

 

 

 

Highlights
 
  •  Autophagy is required for losers of cell competition to be eliminated
 
  •  Autophagy is elevated in prospective loser cells nearby winner cells
 
  •  Elevated autophagy induces hid expression via NFκB
 
  •  Hid cooperates with JNK signaling in loser cells to induce cell death
 
 
Summary
 
Cell competition is a quality control process that selectively eliminates unfit cells from the growing tissue via cell-cell interaction. Despite extensive mechanistic studies, the mechanism by which cell elimination is triggered has been elusive. Here, through a genetic screen in Drosophila, we discover that V-ATPase, an essential factor for autophagy, is required for triggering cell competition. Strikingly, autophagy is specifically elevated in prospective “loser” cells nearby wild-type “winner” cells, and blocking autophagy in loser cells abolishes their elimination. Mechanistically, elevated autophagy upregulates a proapoptotic gene hid through NFκB, and the elevated hid cooperates with JNK signaling to effectively induce loser’s death. Crucially, this mechanism generally applies to cell competition caused by differences in protein synthesis between cells. Our findings establish a common mechanism of cell competition whereby cells with higher protein synthesis induce autophagy in their neighboring cells, leading to elimination of unfit cells.
 
 
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Also tagged with one or more of these keywords: cell competition, autophagy, cell death, jnk, hid, nfκb

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