A bioenergetic profile of non-transformed fibroblasts uncovers a link between death-resistance and enhanced spare respiratory capacity.

ABSTRACT

Apoptosis-resistance and metabolic imbalances are prominent features of cancer cells. We have recently reported on populations of human fibroblasts that exhibit resistance to mitochondrial-mediated apoptosis, acquired as a result of a single genotoxic exposure. The objective of the present study was to investigate the intrinsic bioenergetic profile of the death-resistant cells, as compared to the clonogenic control cells. Therefore, we analyzed the basic bioenergetic parameters including oxygen consumption and extracellular acidification rates, coupling efficiency, and spare respiratory capacity. Our data demonstrate a strong correlation between enhanced spare respiratory capacity and death-resistance, which we postulate to be indicative of the earliest stages of carcinogenesis.