Biologjia Online

The cellular mechanisms for dealing with nutritional stress are remarkably conserved, with the same signaling network used in organisms from yeast to mammals. In one sense, this is not terribly surprising since the most pressing response to such potential injury is always the same: suppress those biochemical reactions that consume energy while at the same time triggering those metabolic pathways most effective at generating ATP. But an interesting problem to contemplate is how this fundamental process has been adapted to the complexities of a multicellular organism in which recognition of the nutritional state is frequently provided by more subtle cues such as hormones or impulses generated within the central nervous system. Moreover, although the cellular responses to nutrient deprivation are conserved phylogenetically, organismal reactions in metazoans are more multifaceted in that one organ often sacrifices for the good of the whole. The major phylogenetically conserved pathway for signaling nutritional stress is now well established as centering on the protein kinase Snf1 in budding yeast, which is orthologous to AMPK-activated protein kinase (AMPK) in higher organisms. As its name suggests, mammalian AMPK is regulated by changes in the ratio of AMP to ATP, a sensitive indicator of the energy state of the cell. Now, three papers report the intriguing observation that an alternative pathway mediated by a Ca2+-dependent protein kinase is also capable of regulating AMPK (Hawley et al., 2005, Hurley et al., 2005 and Woods et al., 2005).