An evolutionary perspective of AMPK–TOR signaling in the three domains of life

Abstract

AMPK and TOR protein kinases are the major control points of energy signaling in eukaryotic cells and organisms. They form the core of a complex regulatory network to co-ordinate metabolic activities in the cytosol with those in the mitochondria and plastids. Despite its relevance, it is still unclear when and how this regulatory pathway was formed during evolution, and to what extent its representations in the major eukaryotic lineages resemble each other. Here we have traced 153 essential proteins forming the human AMPK-TOR pathways across 412 species representing all three domains of life-prokaryotes (bacteria, archaea) and eukaryotes-and reconstructed their evolutionary history. The resulting phylogenetic profiles indicate the presence of primordial core pathways including seven proto-kinases in the last eukaryotic common ancestor. The evolutionary origins of the oldest components of the AMPK pathway, however, extend into the pre-eukaryotic era, and descendants of these ancient proteins can still be found in contemporary prokaryotes. The TOR complex in turn appears as a eukaryotic invention, possibly to aid in retrograde signaling between the mitochondria and the remainder of the cell. Within the eukaryotes, AMPK/TOR showed both a highly conserved core structure and a considerable plasticity. Most notably, KING1, a protein originally assigned as the γ subunit of AMPK in plants, is more closely related to the yeast SDS23 gene family than to the γ subunits in animals or fungi. This suggests its functional difference from a canonical AMPK γ subunit.

The SnRK1 Kinase as Central Mediator of Energy Signaling between Different Organelles

“…Plants have three known Glc-modulated master regulators: HEX-OKINASE1, a direct Glc sensor (Moore et al, 2003;Li and Sheen, 2016); the energy-sensing protein kinase SnRK1, which is inhibited by sugars (Baena-González and Sheen, 2008); and the TARGET OF RAPAMYCIN kinase, which is activated by Glc (Xiong et al, 2013). These major regulators of energy metabolism are evolutionarily highly conserved, and the protokinases can be found in all three domains of life (Roustan et al, 2016). In response to energy deficits, the AMPK/SNF1/ SnRK1 kinases restore energy homeostasis by switching on ATP-producing catabolic pathways (such as glycolysis and fatty acid oxidation), while in parallel switching off biosynthetic and other nonessential ATPconsuming metabolic and growth processes.…”

Quantitative phosphoproteomics reveals the role of the AMPK plant ortholog SnRK1 as a metabolic master regulator under energy deprivation

“…However, it is still unclear if this connection exists in plants, but there is evidence that TOR and SnRK1 pathways have antagonistic roles depending on the energy availability (for review, see refs 23,36,37). …”

Redox state‐dependent modulation of plant SnRK1 kinase activity differs from AMPK regulation in animals

“…In plants, the SNF1‐related protein kinase (SnRK1), an orthologue of the mammalian AMP‐activated protein kinase (AMPK) and yeast SNF1 protein kinase, plays a central role in regulating energy homeostasis, development and various stress responses . SnRK1 is evolutionarily highly conserved and orthologues can be found in all three domains of life . Like its mammalian and yeast counterparts, the SnRK1 protein kinase is a heterotrimeric complex consisting of one catalytic S/T protein kinase ‘alpha’ subunit, and the two regulatory ‘beta’ and ‘gamma’ subunits .…”