title: Glycogen: A must have storage to survive stressful emergencies.
abstract: Mechanisms of adaptation to acute changes in osmolarity are fundamental for life. When exposed to hyperosmotic stress, cells and organisms utilize conserved strategies to prevent water loss and maintain cellular integrity and viability. The production of glycerol is a common strategy utilized by the nematode Caenorhabditis elegans (C. elegans) and many other organisms to survive hyperosmotic stress. Specifically, the transcriptional upregulation of glycerol-3-phosphate dehydrogenase, a rate-limiting enzyme in the production of glycerol, has been previously implicated in many model organisms. However, what fuels this massive and rapid production of glycerol upon hyperosmotic stress has not been clearly elucidated. We have recently discovered an AMPK-dependent pathway that mediates hyperosmotic stress resistance in C. elegans. Specifically, we demonstrated that the chronic activation of AMPK leads to glycogen accumulation, which under hyperosmotic stress exposure, is rapidly degraded to mediate glycerol production. Importantly, we demonstrate that this strategy is utilized by flcn-1 mutant C. elegans nematodes in an AMPK-dependent manner. FLCN-1 is the worm homolog of the human renal tumor suppressor Folliculin (FLCN) responsible for the Birt-Hogg-Dubé neoplastic syndrome. Here, we comment on the dual role for glycogen in stress resistance: it serves as an energy store and a fuel for osmolyte production. We further discuss the potential utilization of this mechanism by organisms in general and by human cancer cells in order to survive harsh environmental conditions and notably hyperosmotic stress.
authors.affiliation: Goodman Cancer Research Center, McGill University, Montréal, Québec, Canada; Department of Biochemistry, McGill University, Montréal, Québec, Canada.
authors.forename: Elite
authors.initials: E
authors.lastname: Possik
authors.affiliation: Goodman Cancer Research Center, McGill University, Montréal, Québec, Canada; Department of Biochemistry, McGill University, Montréal, Québec, Canada.
authors.forename: Arnim
authors.initials: A
authors.lastname: Pause
keywords: AMPK; Folliculin; cancer; glycerol; glycogen; hyperosmotic stress