Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development

Xueping Qu, Zhongju Zou, Qihua Sun, Kate Luby-Phelps, Pengfei Cheng, Robert N. Hogan, Christopher Gilpin, Beth Levine

Research output: Contribution to journalArticle

463 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)931-946
Number of pages16
JournalCell
Volume128
Issue number5
DOIs
StatePublished - Mar 9 2007

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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