A shift to organismal stress resistance in programmed cell death mutants.
Animals have many ways of protecting themselves against stress; for example, they can induce animal-wide, stress-protective pathways and they can kill damaged cells via apoptosis. We have discovered an unexpected regulatory relationship between these two types of stress responses. We find that C. elegans mutations blocking the normal course of programmed cell death and clearance confer animal-wide resistance to a specific set of environmental stressors; namely, ER, heat and osmotic stress. Remarkably, this pattern of stress resistance is induced by mutations that affect cell death in different ways, including ced-3 (cell death defective) mutations, which block programmed cell death, ced-1 and ced-2 mutations, which prevent the engulfment of dying cells, and progranulin (pgrn-1) mutations, which accelerate the clearance of apoptotic cells. Stress resistance conferred by ced and pgrn-1 mutations is not additive and these mutants share altered patterns of gene expression, suggesting that they may act within the same pathway to achieve stress resistance. Together, our findings demonstrate that programmed cell death effectors influence the degree to which C. elegans tolerates environmental stress. While the mechanism is not entirely clear, it is intriguing that animals lacking the ability to efficiently and correctly remove dying cells should switch to a more global animal-wide system of stress resistance.
Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California, United States of America ; Department of Biochemistry, University of California San Francisco, San Francisco, California, United States of America.
Meredith E
ME
Judy
Ayumi
A
Nakamura
Anne
A
Huang
Harli
H
Grant
Helen
H
McCurdy
Kurt F
KF
Weiberth
Fuying
F
Gao
Giovanni
G
Coppola
Cynthia
C
Kenyon
Aimee W
AW
Kao
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009997:Osmotic Pressure; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*
C479695:CED-2 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C422043:ced-1 protein, C elegans; D020169:Caspases; C089223:ced-3 protein, C elegans