"Non-canonical mitochondrial unfolded protein response impairs placental oxidative phosphorylation in early-onset pre-eclampsia": new article published by CTR team (H. Yung, F. Colleoni, E. Dommett, T. Cindrova-Davies, J. Kingdom, A. Murray, and G. Burton) in PNAS.
Preeclampsia endangers the lives and well-being of mother and baby. The syndrome is associated with placental dysfunction. High demand for energy to support active nutrient transport and hormone production increases placental susceptibility to mitochondrial stress. Here, we investigate mitochondrial activity and explore stress-response pathways in preeclamptic placentas. We demonstrate activation of noncanonical mitochondrial unfolded protein response (UPRmt) pathways associated with reduced CLPP, a key protease in UPRmt signalling, that compromises mitochondrial respiration. The changes can be recapitulated in trophoblast cells by hypoxia–reoxygenation. Either activation of UPRmt or knockdown of CLPP can sufficiently reduce mitochondrial respiration. Translation of CLPP is negatively regulated by the endoplasmic reticulum UPR pathway. Understanding mitochondrial stress provides new insights into the pathophysiology of early-onset preeclampsia. (Source: summary copied from PNAS "Significance")
The team's important results identify UPRmt as a therapeutic target for restoration of placental function in early-onset preeclampsia.
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