Preventing cell death with a 'check valve' in mitochondrial complex I?

E Fontaine,G Vial,D Detaille

doi:10.1038/cddis.2016.71

Abstract

Preventing cell death with a 'check valve' in mitochondrial complex I?

Highlights

In our recently published work in Cell Death Discovery,[10] we have reported a hitherto unrecognized situation in which superoxide production driven by the reverse electron transfer is dramatically reduced, without any effect on oxygen consumption of intact cells, on cell energy status and on isolated complex I activity
Using another cell line and another model to induce permeability transition pore (PTP) opening-induced cell death, we recently observed that experimental conditions preventing oxidative stress prevented PTP opening and subsequent cell death induced by the removal of energy substrates.[12]
Metformin—which is not an antioxidant but prevents superoxide production driven by the reverse electron transfer13— prevented PTP opening and subsequent cell death.[12]

Summary

Introduction

In our recently published work in Cell Death Discovery,[10] we have reported a hitherto unrecognized situation in which superoxide production driven by the reverse electron transfer is dramatically reduced, without any effect on oxygen consumption of intact cells, on cell energy status and on isolated complex I activity. Using another cell line and another model to induce PTP opening-induced cell death, we recently observed that experimental conditions preventing oxidative stress (incubation in the absence of oxygen or incubation in the presence of antioxidant N-acetyl-cysteine) prevented PTP opening and subsequent cell death induced by the removal of energy substrates.[12] Interestingly, metformin—which is not an antioxidant but prevents superoxide production driven by the reverse electron transfer13— prevented PTP opening and subsequent cell death.[12] This strongly suggests that such a particular superoxide production is mandatory for permanent PTP opening and for this type of cell death.

Results

Conclusion