TY - JOUR
T1 - Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development
AU - Qu, Xueping
AU - Zou, Zhongju
AU - Sun, Qihua
AU - Luby-Phelps, Kate
AU - Cheng, Pengfei
AU - Hogan, Robert N.
AU - Gilpin, Christopher
AU - Levine, Beth
N1 - Funding Information:
This work was supported by NIH grants R01 CA084254 and CA109618, and an American Cancer Society Grant ACS RSG 98-339 to B.L. We thank Linda Margraf for expert pathological review of mouse lungs; Robert Hammer for helpful suggestions; Yajuan Liu for excellent technical assistance; Tom Januszewski and Laurie Mueller for assistance with electron microscopy; Nancy Stallings for assistance with the ATP assay; Pegah Jalili, Yan Li, and Haydyn Ball for assistance with ESI-MS assays; Noboru Mizushima, Nathaniel Heintz, and Tamotsu Yoshimori for providing reagents; and Frederick Scott and Renee Talley for administrative assistance.
PY - 2007/3/9
Y1 - 2007/3/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2006.12.044
DO - 10.1016/j.cell.2006.12.044
M3 - Article
C2 - 17350577
AN - SCOPUS:33847404337
SN - 0092-8674
VL - 128
SP - 931
EP - 946
JO - Cell
JF - Cell
IS - 5
ER -