Peer-Reviewed Journal Details
Mandatory Fields
Zhdanov, AV;Andreev, DE;Baranov, PV;Papkovsky, DB
2017
May
Free Radical Biology & Medicine
Low energy costs of F1Fo ATP synthase reversal in colon carcinoma cells deficient in mitochondrial complex IV
Validated
WOS: 4 ()
Optional Fields
CANCER-CELLS OXIDATIVE-PHOSPHORYLATION INHIBITOR PROTEIN OXYGEN HEART METABOLISM DEPLETION ISCHEMIA BINDING ARCHITECTURE
106
184
195
Mitochondrial polarisation is paramount for a variety of cellular functions. Under ischemia, mitochondrial membrane potential (Delta Psi m) and proton gradient (Delta pH) are maintained via a reversal of mitochondrial F1Fo ATP synthase (mATPase), which can rapidly deplete ATP and drive cells into energy crisis. We found that under normal conditions in cells with disassembled cytochrome c oxidase complex (COX-deficient HCT116), mATPase maintains Delta Psi m at levels only 15-20% lower than in WT cells, and for this utilises relatively little ATP. For a small energy expenditure, mATPase enables mitochondrial Delta pH, protein import, Ca2+ turnover, and supports free radical detoxication machinery enlarged to protect the cells from oxidative damage. Whereas in COX deficient cells the main source of ATP is glycolysis, the Allfrn is still maintained upon inhibition of the adenine nucleotide translocators with bongitrekic acid and carboxyatractyloside, indicating that the role of ANTs is redundant, and matrix substrate level phosphorylation alone or in cooperation with ATP-Mg/P-i carriers can continuously support the mATPase activity. Intriguingly, we found that mitochondrial complex III is active, and it contributes not only to free radical production, but also to Allfin maintenance and energy budget of COX deficient cells. Overall, this study demonstrates that F1Fo ATP synthase can support general mitochondrial and cellular functions, working in extremely efficient 'energy saving' reverse mode and flexibly recruiting free radical detoxication and ATP producing/transporting pathways.
NEW YORK
0891-5849
10.1016/j.freeradbiomed.2017.02.025
Grant Details