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Ultrasound-stimulated microbubble (USMB) treatment, a technique used to enhance drug delivery to cancer cells by creating temporary pores in cell membranes, causes mitochondrial damage and triggers a cellular survival response called mitophagy (selective degradation of damaged mitochondria). Researchers found that this protective mitophagy process is activated through an AMPK-dependent pathway involving Parkin and PINK1 proteins. When mitophagy was blocked through Parkin silencing or PINK1 inhibition, significantly more cells died following USMB treatment, indicating that mitophagy helps cancer cells survive this therapeutic approach.
Why it matters
The findings suggest that combining USMB cancer therapy with drugs that inhibit mitophagy could improve treatment effectiveness by preventing cancer cells from repairing mitochondrial damage and surviving the therapeutic insult. This could lead to development of more effective combination therapies for solid tumors.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Ultrasound-stimulated microbubble (USMB) sonoporation treatment is an emerging strategy for cancer therapy that enhances drug delivery by perforating the plasma membrane. This membrane permeabilization also causes cellular metabolic stress as cells leak metabolites such as ATP and amino acids. Collectively, cells may die in response to excess membrane damage and stress. However, many cells survive the USMB insult by engaging membrane repair and adaptation pathways such as stimulation of AMPK. In this study, we investigated the impact of USMB treatment on mitochondria and their role in post-exposure cellular survival. We found that USMB causes mitochondrial fragmentation and decreases mitochondrial membrane potential. Subsequently, autophagy and Parkin-dependent mitophagy are triggered post-USMB treatment in an AMPK-dependent mechanism. Importantly, Parkin silencing and PINK1 inhibition augment cell death when combined with USMB exposure, suggesting that mitophagy is an important cell survival process in response to USMB. We propose that combining USMB with inhibitors of mitophagy and metabolic stress adaptation is a strong candidate for therapeutic development to treat solid tumours.
Source: Mitophagy is required for cell survival upon ultrasound and microbubble therapeutic exposure