Plant Vacuolar and Human Endolysosomal Two-Pore Channels: Similarities and Differences

Di Franco E, Milenkovic S, Lagostena L, Meucci M, Festa M, Gradogna A, Dietrich P, Filippini A, Ceccarelli M, Carpaneto A (2026)

Publication Type: Journal article, Review article

Publication year: 2026

Journal

Cells MDPI

Book Volume: 15

Article Number: 675

Journal Issue: 8

DOI: 10.3390/cells15080675

Abstract

Two-pore channels (TPCs) are evolutionarily conserved intracellular cation channels found in both plants and animals, where they mediate ion fluxes across endomembrane compartments. While historically the plant channel was among the first plant ion channels to be characterized, thanks to the relative ease of applying the patch-clamp technique to isolated plant vacuoles, where it is localized, the functional properties of the two main human isoforms, HsTPC1 and HsTPC2, expressed in endosomal and lysosomal membranes, were elucidated much later. In plants, TPCs are typically represented by a single isoform, exemplified by AtTPC1 in the model plant Arabidopsis thaliana, which functions as a voltage-dependent, Ca2+-regulated channel. The physiological role of plant TPCs is not yet fully clarified, although evidence suggests that they may contribute to systemic signaling and stress responses. In humans, two main isoforms, HsTPC1 and HsTPC2, are expressed in endosomal and lysosomal membranes. Human TPCs are primarily regulated by the phosphoinositide PI(3,5)P2 and display a high selectivity for Na+. However, these channels also appear as a non-selective cationic conductance when activated by the potent Ca2+-mobilizing messenger NAADP, likely through interaction with an accessory protein. Functionally, human TPCs are involved in endolysosomal trafficking, membrane fusion, and intracellular signaling, with emerging roles in immunity, metabolism, and disease. Overall, TPCs represent key components of intracellular ion homeostasis and cellular physiology; however, their precise regulatory mechanisms and integrated physiological roles remain only partially understood and, in several respects, are still elusive.

Authors with CRIS profile

Petra Dietrich Professur für Zellbiologie der Pflanzen

Involved external institutions

Università degli studi "La Sapienza" IT Italy (IT) Università degli Studi di Cagliari IT Italy (IT) University of Genova / Università degli Studi di Genova IT Italy (IT) Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy IT Italy (IT)

How to cite

APA:

Di Franco, E., Milenkovic, S., Lagostena, L., Meucci, M., Festa, M., Gradogna, A.,... Carpaneto, A. (2026). Plant Vacuolar and Human Endolysosomal Two-Pore Channels: Similarities and Differences. Cells, 15(8). https://doi.org/10.3390/cells15080675

MLA:

Di Franco, Elisabetta, et al. "Plant Vacuolar and Human Endolysosomal Two-Pore Channels: Similarities and Differences." Cells 15.8 (2026).

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