ATP13A4 Regulates Cellular Sensitivity to Polyamine Toxicity Through SAT1

Researchers have identified the P5-type ATPase ATP13A4 as a transport-dependent regulator of cellular sensitivity to polyamines. Using complementary gain- and loss-of-function cellular models, the study demonstrated that ATP13A4 modulates cellular vulnerability to polyamine toxicity. Specifically, expression of functional ATP13A4 sensitized cells to polyamine-induced loss of viability and cell death.

In contrast, expression of a transport-deficient mutant or depletion of endogenous ATP13A4 conferred protection against polyamine toxicity. The researchers observed that this sensitizing outcome could not be accounted for by extracellular amine oxidation. Furthermore, ATP13A4 expression increased cellular reliance on spermidine/spermine N¹-acetyltransferase 1 (SAT1), and pharmacological inhibition of SAT1 markedly exacerbated polyamine-induced cytotoxicity.

The study also linked ATP13A4-dependent polyamine uptake to the activation of JNK-linked stress signaling pathways, finding that JNK inhibition partially attenuated cell death. Together, the findings demonstrate that ATP13A4-mediated uptake sensitizes cells to polyamines, increasing cellular dependence on SAT1-dependent buffering and engaging stress signaling pathways when polyamine buffering capacity is exceeded.

Subject of Research: Cellular sensitivity to polyamine toxicity regulated by ATP13A4

Article Title: ATP13A4 sensitizes cells to polyamine-induced cytotoxicity in a SAT1-dependent manner

Article References: Meeus, E., Ausloos, E., Van den Haute, C., Eggermont, J., van Veen, S., & Vangheluwe, P. (2026). ATP13A4 sensitizes cells to polyamine-induced cytotoxicity in a SAT1-dependent manner. Amino Acids. https://doi.org/10.1007/s00726-026-03532-2

Image Credits: AI Generated

DOI: 10.1007/s00726-026-03532-2

Keywords: ATP13A4, polyamines, cytotoxicity, SAT1, P5-type ATPase, JNK signaling, polyamine transport, cellular homeostasis, sensitizes, cells, polyamine-induced, SAT1-dependent