Metabolic restructuring during energy-limited states: insights from XXXX embryos and other animals.

@entity1 @entity2199 @entity308 @entity5 @entity3179 @entity19928 @entity519 @entity1167 @entity860 @entity2388
Many life history stages of animals that experience environmental insults enter developmental arrested states that are characterized by reduced cellular proliferation, with or without a concurrent reduction in overall metabolism. In the case of the most profound @entity1167 reported in invertebrates, i.e., anaerobic quiescence in @entity19928 embryos, acidification of the intracellular milieu is a major factor governing catabolic and anabolic downregulation. Release of ions from intracellular compartments is the source for approximately 50% of the proton equivalents needed for the 1.5 unit acidification that is observed. Recovery from the @entity1167 requires re-sequestration of the protons with a vacuolar-type ATPase (V-ATPase). The remarkable facet of this mechanism is the ability of embryonic cells to survive the dissipation of intracellular ion gradients. Across many diapause-like states, the metabolic reduction and subsequent matching of energy demand is accomplished by shifting energy metabolism from oxidative phosphorylation to aerobic glycolysis. Molecular pathways that are activated to induce these resilient hypometabolic states include stimulation of the @entity860 -activated protein kinase (AMPK) and insulin signaling via suite of daf (dauer formation) genes for diapause-like states in @entity2199 and insects. Contributing factors for other metabolically @entity308 states involve @entity519 -inducible factor-1 and downregulation of the @entity2388 dehydrogenase complex. Metabolic similarities between natural states of @entity3179 and some @entity5 phenotypes are noteworthy. Reduction of flux through oxidative phosphorylation helps prevent cell death in certain @entity5 types, similar to the way it increases viability of dauer stages in @entity2199 . Mechanisms that underlie natural @entity3179 are being used to pre-condition @entity1 cells prior to cell biostabilization and storage.
