TY - JOUR
T1 - PQM-1 controls hypoxic survival via regulation of lipid metabolism
AU - Heimbucher, Thomas
AU - Hog, Julian
AU - Gupta, Piyush
AU - Murphy, Coleen T.
N1 - Funding Information:
This work was supported by the NIH NIA 1R56AG047344-01A1 293 (C.T.M.) and the Glenn Foundation for Medical Research. C.T.M. is the Director of the Glenn Center for Aging Research at Princeton, which also supports T.H. We thank the Caenorhabditis Genetics center for providing C. elegans strains, and Jasmine Ashraf for technical assistance. Princeton University MicroArray database (PUMAdb) is funded in part by the National Institute of General Medical Sciences (NIGMS) [NIH grant P50 GM071508]. We thank Justus Kleifeld for performing hypoxic glove box experiments, Prof. Ralf Baumeister and members of his laboratory for substantial support to complete this study. We also thank members of the C.T.M. laboratory for comments on the paper.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Animals have evolved responses to low oxygen conditions to ensure their survival. Here, we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial sugar metabolism enzyme. PQM-1 promotes hypoxic fat metabolism by maintaining the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity positively regulates fat transport to developing oocytes through vitellogenins under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in which PQM-1 controls a trade-off between lipid metabolic activity in the mother and her progeny to promote the survival of the species under hypoxic conditions.
AB - Animals have evolved responses to low oxygen conditions to ensure their survival. Here, we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial sugar metabolism enzyme. PQM-1 promotes hypoxic fat metabolism by maintaining the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity positively regulates fat transport to developing oocytes through vitellogenins under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in which PQM-1 controls a trade-off between lipid metabolic activity in the mother and her progeny to promote the survival of the species under hypoxic conditions.
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U2 - 10.1038/s41467-020-18369-w
DO - 10.1038/s41467-020-18369-w
M3 - Article
C2 - 33009389
AN - SCOPUS:85091839634
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4627
ER -