Calcium (Ca

Andrea Puebla-Huerta, Hernán Huerta, Camila Quezada-Gutierez, Pablo Morgado-Cáceres, César Casanova-Canelo, Sandra A Niño, Sergio Linsambarth, Osman Díaz-Rivera, José Alberto López-Domínguez, Sandra Rodríguez-López, José Antonio González-Reyes, Galdo Bustos, Eduardo Silva-Pavez, Alenka Lovy, Gabriel Quiroz, Catalina González-Seguel, Edison Salas-Huenuleo, Marcelo J Kogan, Jordi Molgó, Armen Zakarian, José M Villalba, Christian Gonzalez-Billault, Tito Cali, Ulises Ahumada-Castro, J César Cárdenas

Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile. · pubmed

Paper

Abstract

Therapy-induced senescence (TIS) alters calcium (Ca²⁺) flux and Mitochondria-ER Contact Sites (MERCS), revealing critical vulnerabilities in senescent cells. In this study, TIS was induced using Doxorubicin and Etoposide, resulting in an increased MERCS contact surface but a significant reduction in ER-mitochondria Ca²⁺ flux. Mechanistically, TIS cells exhibit decreased expression of IP3R isoforms and reduced interaction between type 1 IP3R and VDAC1, impairing Ca²⁺ transfer. This flux is crucial for maintaining the viability of senescent cells, highlighting its potential as a therapeutic target. Inhibition of ER-mitochondria Ca²⁺ flux demonstrates senolytic effects both in vitro and in vivo, offering a novel strategy for targeting senescent cells.

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Research summary

Inhibition of ER-mitochondria Ca²⁺ flux demonstrates senolytic effects both in vitro and in vivo. The study addresses the mechanisms of therapy-induced senescence and identifies potential therapeutic targets that could contribute to the understanding and treatment of aging-related cellular dysfunction.

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