Activation of pyruvate dehydrogenase during cuproptosis

A copper-induced cell death, cuproptosis, plays a key role in cancer but mechanism is not well understood.

The researchers develop Mito-TPCA, a live cell mitochondrial thermal profiling strategy, to reveal protein interaction dynamics during cuproptosis. 

They uncover that copper disrupts pyruvate dehydrogenase kinases - pyruvate dehydrogenase (PDK-PDH) associations, leading to PDH dephosphorylation and aberrant activation, which drives cell death and underlies cancer cell susceptibility— highlighting a therapeutic target and tool for mitochondrial proteomics.

https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00708-9

https://sciencemission.com/Mitochondrial-thermal-proteome-profiling