Branched‐chain amino acid synthesis is coupled to TOR activation early in the cell cycle in yeast

Abstract

How cells coordinate their metabolism with division determines the rate of cell proliferation. Dynamic patterns of metabolite synthesis during the cell cycle are unexplored. We report the first isotope tracing analysis in synchronous, growing budding yeast cells. Synthesis of leucine, a branched‐chain amino acid (BCAA), increases through the G1 phase of the cell cycle, peaking later during DNA replication. Cells lacking Bat1, a mitochondrial aminotransferase that synthesizes BCAAs, grow slower, are smaller, and are delayed in the G1 phase, phenocopying cells in which the growth‐promoting kinase complex TORC1 is moderately inhibited. Loss of Bat1 lowers the levels of BCAAs and reduces TORC1 activity. Exogenous provision of valine and, to a lesser extent, leucine to cells lacking Bat1 promotes cell division. Valine addition also increases TORC1 activity. In wild‐type cells, TORC1 activity is dynamic in the cell cycle, starting low in early G1 but increasing later in the cell cycle. These results suggest a link between BCAA synthesis from glucose to TORC1 activation in the G1 phase of the cell cycle. image Branched‐chain amino acid (BCAA) synthesis regulates the activity of TORC1, the master regulator of anabolism, as yeast cells progress in the cell cycle. This provides new insights into how cells coordinate their metabolism with division. Synthesis of leucine increases through the G1 phase of the cell cycle, peaking later during DNA replication. Cells lacking the Bat1 aminotransferase are delayed in the G1 phase and have lower TORC1 activity. TORC1 activity is dynamic in the cell cycle, starting low in early G1 but increasing later in the cell cycle.