Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development

Xueping Qu; Zhongju Zou; Qihua Sun; Katherine Luby‐Phelps; Pengfei Cheng; R. Nick Hogan; Christopher J. Gilpin; Beth Levine

doi:10.1016/j.cell.2006.12.044

Abstract

Autophagy is commonly observed in metazoan organisms during programmed cell death (PCD), but its function in dying cells has been unclear. We studied the role of autophagy in embryonic cavitation, the earliest PCD process in mammalian development. Embryoid bodies (EBs) derived from cells lacking the autophagy genes, atg5 or beclin 1, fail to cavitate. This defect is due to persistence of cell corpses, rather than impairment of PCD. Dying cells in autophagy gene null EBs fail to express the "eat-me" signal, phosphatidylserine exposure, and secrete lower levels of the "come-get-me" signal, lysophosphatidylcholine. These defects are associated with low levels of cellular ATP and are reversed by treatment with the metabolic substrate, methylpyruvate. Moreover, mice lacking atg5 display a defect in apoptotic corpse engulfment during embryonic development. We conclude that autophagy contributes to dead-cell clearance during PCD by a mechanism that likely involves the generation of energy-dependent engulfment signals.

Keywords

AutophagyATG5BiologyCell biologyProgrammed cell deathEmbryonic stem cellApoptosisGeneGenetics

MeSH Terms

Adenosine TriphosphateAnimalsApoptosisApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 5Beclin-1Cell Culture TechniquesCell DifferentiationCell LineCell MembraneCellsCulturedCitric Acid CycleEmbryonic DevelopmentEmbryonic Stem CellsEndodermHumansLungLysophosphatidylcholinesMiceMicrotubule-Associated ProteinsPhagocytosisPhosphatidylserinesProteinsPyruvic AcidRetinaSignal Transduction

Affiliated Institutions

The University of Texas Southwestern Medical Center US

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Publication Info

Year: 2007
Type: article
Volume: 128
Issue: 5
Pages: 931-946
Citations: 639
Access: Closed

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APA Style

                            
                                
                                    Xueping Qu, 
                                
                                    Zhongju Zou, 
                                
                                    Qihua Sun
                                
                                et al.
                            
                            (2007). 
                            Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development. 
                            Cell
                            , 128
                            (5)
                            , 931-946.
                            https://doi.org/10.1016/j.cell.2006.12.044
                        

Identifiers

DOI: 10.1016/j.cell.2006.12.044
PMID: 17350577

Data Quality

Data completeness: 90%