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ROS-induced cytosolic release of mitochondrial PGAM5 accelerates colorectal cancer progression via MST3-mediated YAP activation

GSE249865 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/11/05 Platform GPL24676
Summary
Aberrant mtROS release in response to mitochondrial stress are considered to be a major novel feature of neoplastic transformation. However, the molecular mechanisms by which mtROS contribute to CRC development have not been fully elucidated. In this study, we showed that upon sensing the mtROS signal, the mitochondrially localized phosphatase PGAM5 undergoes cleavage in the mitochondrial transmembrane domain, and then the Cleaved PGAM5 is released into the cytoplasm. Subsequently, Cleaved PGAM5 binds to the kinase MST3 in the cytoplasm to promote MST3 dephosphorylation, resulting in a decrease in MST3 activity. Importantly, MST3 inactivation failed to regulate YAP phosphorylation, leading to YAP translocation into the nucleus, consequently promoting CRC proliferation and metastasis. Collectively, our findings identified the PGAM5-MST3-YAP axis as an important molecular mechanism through which mtROS promotes CRC development.
Published in
ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3
Wang S, Wu X, Bi W et al. · Nature communications 2025 · PMID 39915446 · doi:10.1038/s41467-025-56444-2
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Also filed as BioProject PRJNA1051049 and SRA study SRP477304. Searching any of these in the dataset finder brings you back here.

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