New Insights into Lysosome Destabilization and Iron-Dependent Cell Death in Cancer

Recent research has uncovered a critical link between lysosome stability and iron-dependent cell death, known as ferroptosis, in cancer cells. This process involves the peroxidation of lipids within lysosomes, organelles responsible for degrading and recycling cellular components. Lipid oxidation leads to lysosomal membrane permeabilization, enabling the leakage of iron, which fuels further lipid peroxidation and cell death. This mechanism is especially significant in cancer treatment, as some cancer cells exhibit resistance to ferroptosis, making them harder to eliminate.

The study, conducted by researchers at Kyushu University, utilized both cultured cells and mouse models to visualize where ferroptosis begins within the cell. They discovered that lipid peroxidation in lysosomes acts as a pivotal step in initiating ferroptosis. Interestingly, lipid peroxidation occurred in lysosomes of resistant cancer cells without causing membrane damage unless agents like chloroquine were used to promote lysosomal rupture. This suggests potential strategies to induce ferroptosis even in resistant cancer types.

Professor Ken-ichi Yamada explained that understanding the origin of lipid peroxidation in ferroptosis helps develop targeted therapies. They developed a method to visualize lipid radicals and confirmed that lysosomal membrane permeabilization facilitates the spread of cell death signals. The research further indicates that manipulating lysosomal stability with drugs such as chloroquine could enhance ferroptosis, offering new avenues for cancer treatment.

The findings contribute to the broader goal of harnessing ferroptosis as a therapeutic tool, especially for cancers that evade conventional cell death pathways. Future research aims to unravel why some cells resist lysosomal damage during ferroptosis and how to overcome this resistance for effective therapies.

Source: https://medicalxpress.com/news/2025-05-lysosome-destabilization-iron-cell-death.html