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bioRxiv · 10.1101/769927

PQM-1 controls hypoxic survival via regulation of lipid metabolism

Heimbucher, T.·Hog, J.·Murphy, C. T.
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Abstract

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 enzyme for sugar metabolism. PQM-1 promotes intestinal fat metabolism by activating the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity enhances fat accumulation in embryos 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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Heimbucher, T., Hog, J., Murphy, C. T.. 2019-09-14. PQM-1 controls hypoxic survival via regulation of lipid metabolism. https://doi.org/10.1101/769927

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