Calcium (Ca2+) fluxes at Mitochondria-ER Contact Sites (MERCS) are a new target of senolysis in Therapy-Induced Senescence (TIS).

Puebla-Huerta, A.; Huerta, H.; Quezada-Gutierrez, C.; Morgado-Caceres, P.; Casanova-Canelo, C.; Linsambarth, S.; Diaz-Rivera, O.; Lopez-Dominguez, J. A.; Rodriguez-Lopez, S.; Bustos, G.; Silva-Pavez, E.; Lovy, A.; Quiroz, G.; Gonzalez-Seguel, C.; Salas-Huenuleo, E.; Kogan, M.; Molgo, J.; Zakarian, A.; Villalba, J. M.; Gonzalez-Billault, C.; Ahumada-Castro, U.; Cardenas, J. C.

doi:10.1101/2024.03.31.587471

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bioRxiv · 10.1101/2024.03.31.587471

Calcium (Ca2+) fluxes at Mitochondria-ER Contact Sites (MERCS) are a new target of senolysis in Therapy-Induced Senescence (TIS).

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Abstract

O_LIThis study investigates the state of calcium (Ca2+) flux and Mitochondria-ER contact sites (MERCS) on Therapy-Induced Senescence (TIS). C_LIO_LITIS cells-induced by Doxorubicin and Etoposide increase their MERCS contact surface but exhibit a decreased ER-mitochondria Ca2+ flux. C_LIO_LITIS cells show decreased levels of IP3R isoforms and a decreased interaction between type 1 IP3R isoform and VDAC1. C_LIO_LIThe ER-mitochondria Ca2+ flux is essential to maintain the viability of senescence cells. C_LIO_LIInhibition of ER-mitochondria Ca2+ flux rise as a new target of senolysis in vitro and in vivo. C_LI

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Puebla-Huerta, A., Huerta, H., Quezada-Gutierrez, C., Morgado-Caceres, P., Casanova-Canelo, C., Linsambarth, S., Diaz-Rivera, O., Lopez-Dominguez, J. A., Rodriguez-Lopez, S., Bustos, G., Silva-Pavez, E., Lovy, A., Quiroz, G., Gonzalez-Seguel, C., Salas-Huenuleo, E., Kogan, M., Molgo, J., Zakarian, A., Villalba, J. M., Gonzalez-Billault, C., Ahumada-Castro, U., Cardenas, J. C.. 2024-04-01. Calcium (Ca2+) fluxes at Mitochondria-ER Contact Sites (MERCS) are a new target of senolysis in Therapy-Induced Senescence (TIS).. https://doi.org/10.1101/2024.03.31.587471

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