Cells that die via AP-3 complex-dependent regulated death pathway support survivors under amino acid deficiency

There are examples of starvation initiating a programmed death cascade in unicellular organisms. It is believed that individuals committing suicide in this way support the survivors with their nutrients. It was recently discovered that heating up to 51°C kills the yeast Saccharomyces cerevisiae cells in a special way. The cells dying from such heating first decompose the lysosome membrane, and only a few hours later lose the integrity of the plasma membrane. Since lysosomes contain hydrolases of nitrogen-containing biopolymers, this suicide pathway could help survivors under conditions of nitrogen starvation. The fact is that after the destruction of the plasma membrane, the salt composition of the cytosol changes abruptly, which in turn can lead to the aggregation of nitrogen-containing macromolecules, proteins and nucleic acids. The pores of the yeast cell walls are too small to let such aggregates through. Our experimental data are consistent with this hypothesis. We have shown that cells killed by heating up to (in our case) 52°C stimulate the growth of living cells under amino acid deficiency conditions. AP-3 complex mutants, which are unable to destroy the lysosome membrane, do not have this ability. Cells killed by boiling also do not support growth under these conditions. Unexpectedly, the medium from cells killed by boiling contained, on average, more of each amino acid than the medium from cells killed by heating to 52°C. Nevertheless, spectrophotometry and mass spectrometric analysis showed that the medium after heating to 52°C was richer in terms of the content of substances absorbing light with a short wavelength. We assume that mass hydrolysis of nucleic acids supports the growth of surviving cells under conditions of deficiency of an available nitrogen source.

AP-3 complex, nitrogen starvation, regulated cell death, vacuole, yeast