Mitochondrial bioenergetics-SASP crosstalk determines senolytic efficacy in therapy-induced senescence.

ABSTRACT: Mitochondria integrate senescence and apoptotic fates, yet it is unclear whether their ability to oxidize different fuels for energy production influences their vulnerability to senolytics in therapy-induced senescence (TIS). Using MitoPlates™ technology, we functionally mapped the mitophenotypes of TIS cancer cells by quantifying electron transport chain (ETC) flux from various NADH/FADH₂ substrates. We then related these profiles to the responsiveness of TIS cancer cells to BCL-xL-targeting BH3 senolytics, as well as to inflammatory SASP signaling sensed by an NF-κB/miR-146a reporter. Mechanistically distinct senogenic stressors produced markedly different bioenergetic outputs and substrate diversity, establishing mitochondria as an emergent, stress-encoded property of TIS phe

SUBMITTER: Llop-Hernandez A 

PROVIDER: S-EPMC12949218 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature