Mitochondrial consumption of cytosolic ATP: Not so fast

In various pathologic circumstances depolarized mitochondria are thought to precipitate cell death by avidly consuming cytosolic ATP. However, for as long as the inner mitochondrial membrane remains intact the reversal potentials of the adenine nucleotide translocase (ANT) and that of F(0)-F(1) ATP synthase are strategically positioned so that they oppose import of cytosolic ATP into the matrix of respiration-impaired mitochondria. This arrangement also seems to protect against a hysteretic consumption of cytosolic ATP accumulating in the mitochondrial matrix, in view of the depolarization caused by inhibition of F(0)-F(1) ATP synthase by the endogenous protein IF1, yielding fast ANT reversal rates. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.