Spermidine is a type of molecule called a adenosine-receptor expression and function forged in life; what other chains are forged in polyamine. It is mainly produced from a meta- between the species8, and therefore efforts to cell death? bolic pathway that converts the amino acid use these metabolites to treat human disease arginine to polyamines through intermediates might prove challenging. Douglas R. Green is in the Department of that include the molecule ornithine (Fig. 1). Medina and colleagues’ work opens rich Immunology, St. Jude Children’s Research Medina and colleagues traced the conversion possibilities for future investigations into Hospital, Memphis, Tennessee 38105, USA. of arginine to spermidine by this pathway, and how apoptosis triggers metabolic changes, e-mail:
[email protected] found that cells induced to undergo apoptosis and how the regulated release of metabolites increased their synthesis of spermidine and its influences tissues. In contrast to apoptosis, 1. Medina, C. B. et al. Nature 580, 130–135 (2020). precursor, the molecule putrescine, before other forms of cell death, such as regulated 2. Green, D. R. Cell Death: Apoptosis and Other Means to an dying. The apoptotic cells released spermi- forms of necrosis, have profoundly different End 2nd edn (Cold Spring Harb. Lab. Press, 2018). 3. Lüthi, A. U. & Martin, S. J. Cell Death Differ. 14, 641–650 dine, but not putrescine. Spermidine release effects on surrounding cells, and whether (2007). occurred in a PANX1-dependent manner. and how changes in metabolism triggered 4. Kerr, J. F. R., Wyllie, A. H. & Currie, A. R. Br. J. Cancer 26, Although this phenomenon was monitored by those cell-death pathways influence their 239–257 (1972).