Proceedings of the National Academy of Sciences· 2026Q1
Membrane contact activation of Piezo2 drives lysosome–mitochondrion Ca 2+ transfer and signaling in Trypanosoma cruzi
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- Q1SCImago
- 2026year
Short summary
A novel lysosome-to-mitochondrion calcium (Ca2+) transfer pathway in Trypanosoma cruzi, mediated by the mechano/osmosensitive channel TcPiezo2, has been identified, directly regulating mitochondrial bioenergetics and parasite survival.
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Key points
- A lysosome-to-mitochondrion Ca2+ transfer pathway, regulated by TcPiezo2, exists in Trypanosoma cruzi.
- TcPiezo2 channels at lysosome-mitochondrion contact sites (LMCs) initiate Ca2+ release from lysosomes.
- This Ca2+ flux drives mitochondrial Ca2+ uptake, impacting parasite metabolism and redox homeostasis.
- Disruption of TcPiezo2-mediated Ca2+ transfer leads to impaired mitochondrial bioenergetics and parasite death.
AI-generated from the title and abstract; the full text is not read.
Abstract
Calcium ion (Ca 2+ ) transfer from other organelles is central to mitochondrial metabolism and cell survival, yet how mechanical forces regulate interorganelle communication remains unclear. Here we report a lysosome-to-mitochondrion pathway in Trypanosoma cruzi , the etiologic agent of Chagas disease, mediated by the mechano/osmosensitive channel TcPiezo2. Using ultrastructural, biochemical, and live-cell superresolution imaging, we define lysosome–mitochondrion contact sites (LMCs) that enable direct Ca 2+ transfer. TcPiezo2 triggers Ca 2+ release, which generates perilysosomal nanodomains that drives mitochondrial Ca 2+ uptake via the voltage-dependent anion channel and the mitochondrial Ca 2+ uniporter complex. Disruption of TcPiezo2-dependent Ca 2+ transfer impairs mitochondrial metabolism, perturbs redox homeostasis, induces autophagy, and eventually leads to parasite death. These findings establish LMCs as a signaling platform that directly regulates interorganelle Ca 2+ transfer and mitochondrial bioenergetics.
The authors' abstract, as published at the source. Proceedings of the National Academy of Sciences, 2026 · DOI ↗
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PhysiologyBiochemistry, Genetics and Molecular Biology