Mechanosensitive ion channels in apoptosis and ferroptosis: focusing on the role of Piezo1

Mechanosensitive ion channels sense mechanical stimuli applied directly to the cellular membranes or indirectly through their tethered components, provoking cellular mechanoresponses. Among others, Piezo1 mechanosensitive ion channel is a re-latively novel Ca2+-permeable channel that is primarily present in non-sensory tissues. Recent studies have demonstrated that Piezo1 plays an important role in Ca2+-dependent cell death, including apoptosis and ferroptosis, in the presence of mecha-nical stimuli. It has also been proven that cancer cells are sensitive to mechanical stresses due to higher expression levels of Piezo1 compared to normal cells. In this review, we discuss Piezo1-mediated cell death mechanisms and therapeutic strate-gies to inhibit or induce cell death by modulating the activity of Piezo1 with pharmacological drugs or mechanical perturba-tions induced by stretch and ultrasound. [BMB Reports 2023; 56(3): 145-152]

Automated summary

Mechanosensitive ion channels can detect mechanical stimuli directly applied to cellular membranes or indirectly through tethered components, leading to cellular mechanoresponses. Among these channels, Piezo1 is a relatively new Ca2+-permeable channel primarily found in non-sensory tissues. Recent studies have shown that Piezo1 plays a crucial role in Ca2+-dependent cell death, including apoptosis and ferroptosis, in the presence of mechanical stimuli. Cancer cells are also sensitive to mechanical stresses due to higher levels of Piezo1 expression compared to normal cells. This review discusses Piezo1-mediated cell death mechanisms and therapeutic strategies to modulate Piezo1 activity using pharmacological drugs or mechanical perturbations induced by stretch and ultrasound.