Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS)

Andrea Puebla-Huerta; Hernán Huerta; Camila Quezada-Gutierez; Pablo Morgado-Cáceres; César Casanova-Canelo; Sandra A. Niño; Sergio Linsambarth; Osman Diaz Rivera; José Alberto López-Domínguez; SANDRA RODRIGUEZ-LOPEZ; José A. 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 Manuel Villalba Montoro; Christian Gonzalez-Billault; Tito Cali; Ulises Ahumada-Castro; Cesar Cardenas

Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS)

Andrea Puebla-Huerta
, Hernán Huerta
, Camila Quezada-Gutierez
, Pablo Morgado-Cáceres
, César Casanova-Canelo
, Sandra A. Niño
, Sergio Linsambarth
, Osman Diaz Rivera
, José Alberto López-Domínguez
, SANDRA RODRIGUEZ-LOPEZ
, José A. 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 Manuel Villalba Montoro, Christian Gonzalez-Billault, Tito Cali, Ulises Ahumada-Castro^*, Cesar Cardenas^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English
Article number	11
Journal	npj Aging
Volume	11
Issue number	1
State	Published - 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Cite this

Puebla-Huerta, A., Huerta, H., Quezada-Gutierez, C., Morgado-Cáceres, P., Casanova-Canelo, C., Niño, S. A., Linsambarth, S., Rivera, O. D., López-Domínguez, J. A., RODRIGUEZ-LOPEZ, SANDRA., González-Reyes, J. A., Bustos, G., Silva-Pavez, E., Lovy, A., Quiroz, G., González-Seguel, C., Salas-Huenuleo, E., Kogan, M. J., Molgó, J., ... Cardenas, C. (2025). Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS). npj Aging, 11(1), Article 11.

@article{9a4896e067724e46a646cc59d2faca62,

title = "Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS)",

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.",

author = "Andrea Puebla-Huerta and Hern{\'a}n Huerta and Camila Quezada-Gutierez and Pablo Morgado-C{\'a}ceres and C{\'e}sar Casanova-Canelo and Ni{\~n}o, \{Sandra A.\} and Sergio Linsambarth and Rivera, \{Osman Diaz\} and L{\'o}pez-Dom{\'i}nguez, \{Jos{\'e} Alberto\} and SANDRA RODRIGUEZ-LOPEZ and Gonz{\'a}lez-Reyes, \{Jos{\'e} A.\} and Galdo Bustos and Eduardo Silva-Pavez and Alenka Lovy and Gabriel Quiroz and Catalina Gonz{\'a}lez-Seguel and Edison Salas-Huenuleo and Kogan, \{Marcelo J.\} and Jordi Molg{\'o} and Armen Zakarian and Montoro, \{Jos{\'e} Manuel Villalba\} and Christian Gonzalez-Billault and Tito Cali and Ulises Ahumada-Castro and Cesar Cardenas",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

language = "English",

volume = "11",

journal = "npj Aging",

issn = "2056-3973",

publisher = "Nature Research",

number = "1",

}

Puebla-Huerta, A, Huerta, H, Quezada-Gutierez, C, Morgado-Cáceres, P, Casanova-Canelo, C, Niño, SA, Linsambarth, S, Rivera, OD, López-Domínguez, JA, RODRIGUEZ-LOPEZ, SANDRA, González-Reyes, JA, Bustos, G, Silva-Pavez, E, Lovy, A, Quiroz, G, González-Seguel, C, Salas-Huenuleo, E, Kogan, MJ, Molgó, J, Zakarian, A, Montoro, JMV, Gonzalez-Billault, C, Cali, T, Ahumada-Castro, U & Cardenas, C 2025, 'Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS)', npj Aging, vol. 11, no. 1, 11.

TY - JOUR

T1 - Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS)

AU - Puebla-Huerta, Andrea

AU - Huerta, Hernán

AU - Quezada-Gutierez, Camila

AU - Morgado-Cáceres, Pablo

AU - Casanova-Canelo, César

AU - Niño, Sandra A.

AU - Linsambarth, Sergio

AU - Rivera, Osman Diaz

AU - López-Domínguez, José Alberto

AU - RODRIGUEZ-LOPEZ, SANDRA

AU - González-Reyes, José A.

AU - Bustos, Galdo

AU - Silva-Pavez, Eduardo

AU - Lovy, Alenka

AU - Quiroz, Gabriel

AU - González-Seguel, Catalina

AU - Salas-Huenuleo, Edison

AU - Kogan, Marcelo J.

AU - Molgó, Jordi

AU - Zakarian, Armen

AU - Montoro, José Manuel Villalba

AU - Gonzalez-Billault, Christian

AU - Cali, Tito

AU - Ahumada-Castro, Ulises

AU - Cardenas, Cesar

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85218704942

M3 - Article

SN - 2056-3973

VL - 11

JO - npj Aging

JF - npj Aging

IS - 1

M1 - 11

ER -

Calcium (Ca2+) fluxes at mitochondria-ER contact sites (MERCS) are a new target of senolysis in therapy-induced senescence (TIS)

Abstract

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