Amino Acid Signaling for TOR in Eukaryotes: Sensors, Transducers, and a Sustainable Agricultural fuTORe.

Nanticha Lutt,Jacob O Brunkard

doi:10.3390/biom12030387

Abstract

Eukaryotic cells monitor and regulate metabolism through the atypical protein kinase target of rapamycin (TOR) regulatory hub. TOR is activated by amino acids in animals and fungi through molecular signaling pathways that have been extensively defined in the past ten years. Very recently, several studies revealed that TOR is also acutely responsive to amino acid metabolism in plants, but the mechanisms of amino acid sensing are not yet established. In this review, we summarize these discoveries, emphasizing the diversity of amino acid sensors in human cells and highlighting pathways that are indirectly sensitive to amino acids, i.e., how TOR monitors changes in amino acid availability without a bona fide amino acid sensor. We then discuss the relevance of these model discoveries to plant biology. As plants can synthesize all proteinogenic amino acids from inorganic precursors, we focus on the possibility that TOR senses both organic metabolites and inorganic nutrients. We conclude that an evolutionary perspective on nutrient sensing by TOR benefits both agricultural and biomedical science, contributing to ongoing efforts to generate crops for a sustainable agricultural future.

Highlights

Target of rapamycin (TOR) is a serine/threonine kinase that senses environmental cues, especially nutrient availability, to coordinate eukaryotic cellular metabolism [1–5].TOR supports growth by activating anabolic processes, such as mRNA translation [6–9], nucleotide biosynthesis [10–13], and lipid biosynthesis [14–16], while inhibiting catabolic processes, such as autophagy [17–21]
The stimulatory effect of amino acids on TOR has primarily been studied in heterotrophs, especially yeast, invertebrates, and mammals, that rely on dietary sources for the 20 proteinogenic amino acids
TOR is responsive to amino acid signals in autotrophic plants [27–30], but the precise amino acids sensed by TOR and the molecular mechanisms of amino acid sensing in plants remain unknown

Summary

Introduction

Target of rapamycin (TOR) is a serine/threonine kinase that senses environmental cues, especially nutrient availability, to coordinate eukaryotic cellular metabolism [1–5]. The stimulatory effect of amino acids on TOR has primarily been studied in heterotrophs, especially yeast, invertebrates, and mammals, that rely on dietary sources for the 20 proteinogenic amino acids. Unlike these model species, plants are autotrophs that can synthesize all proteinogenic amino acids from inorganic precursors [24–26]. We summarize the current understanding of the molecular pathways of amino acid sensing by TOR in mammalian, invertebrate, and yeast models, discuss the recent literature on amino acid sensing by TOR in plants, address the possibility that TOR responds to both inorganic and organic nitrogenous compounds in plant cells, and propose that a deeper understanding of nitrogen–TOR signaling is urgently needed to minimize reliance on chemical fertilizers for a sustainable agricultural future. Biomolecules 2022, 12, 387 argue that a comparative, evolutionary perspective on nutrient sensing by TOR benefits both agricultural and biomedical science, and we highlight how ongoing studies of TOR signaling in plants and algae contribute to these fields

Sensors and Transducers in Metabolic Signaling

Plant Nutrient Sensing