Organelle acidification has essential implications for the development of degenerative disorders in the brain and heart, but the experimental characterization of these dynamic compartments in native-like contexts is challenging. Computational models can help organize and refine putative mechanisms of organelle acidifications in the same way they helped with brain and heart electrophysiology. Unfortunately, existing models of organelle acidification are not easy to access and operate. Here, we ported the existing model of lysosome acidification into an open-source Python implementation. Furthermore, we hosted this implementation in Google Colab, so everyone with a browser can simulate organelle acidification without a technical background. Finally, we demonstrate how this model can be extended to new organelle types by providing simulations of synaptic vesicle acidification and filling that incorporate different proposed modes of transport and can be fitted to recent experiments.

An open-science computational model of organelle acidification to integrate putative mechanisms of synaptic vesicle acidification and filling / Baraglia, Emanuele Carnevale; Fattorini, Giorgia; Chattaraj, Sandipan; Pasqualini, Francesco; Conti, Fiorenzo. - In: NEUROCHEMICAL RESEARCH. - ISSN 0364-3190. - 50:3(2025). [10.1007/s11064-025-04432-9]

An open-science computational model of organelle acidification to integrate putative mechanisms of synaptic vesicle acidification and filling

Fattorini, Giorgia
Co-primo
;
Pasqualini, Francesco
Penultimo
;
Conti, Fiorenzo
Ultimo
2025-01-01

Abstract

Organelle acidification has essential implications for the development of degenerative disorders in the brain and heart, but the experimental characterization of these dynamic compartments in native-like contexts is challenging. Computational models can help organize and refine putative mechanisms of organelle acidifications in the same way they helped with brain and heart electrophysiology. Unfortunately, existing models of organelle acidification are not easy to access and operate. Here, we ported the existing model of lysosome acidification into an open-source Python implementation. Furthermore, we hosted this implementation in Google Colab, so everyone with a browser can simulate organelle acidification without a technical background. Finally, we demonstrate how this model can be extended to new organelle types by providing simulations of synaptic vesicle acidification and filling that incorporate different proposed modes of transport and can be fitted to recent experiments.
2025
Computational models, Organelle acidification, Synaptic vesicles, VGAT, VGLUT1
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/345272
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