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Low Mitochondrial Proton Leak Due to High Membrane Cholesterol Content and Cytosolic Creatine Kinase as Two Features of the Deviant Bioenergetics of Ehrlich and AS30-D Tumor Cells¹

Université Lyon 1, F-69622 Villeurbanne Cedex, France

Isolated mitochondria from highly glycolytic Ehrlich and AD30-D tumor cells have a 12.4- and a 2.3-fold higher cholesterol level, respectively, than that of rat liver mitochondria. The passive proton permeability of Ehrlich and AS30-D tumor inner membrane mitochondria is, respectively, 4- and 1.4-fold lower than that of rat liver mitochondrial membrane. This feature is accompanied by a lower proton leak current in tumor mitochondria. A 3.5-fold cholesterol enrichment of rat liver mitochondria decreases their passive proton permeability by a factor of 2, thus establishing a direct relationship between the cholesterol contents of mitochondrial membranes and the passive proton permeability. Creatine kinase activity is present in the cytosol of these cells and is mostly represented by the BB isoform. Since AS30-D tumor cells' treatment with the creatine analogue ß-guanidinopropionic acid decreases their life span and viability, creatine kinase is an indispensable enzyme entering a main energy distribution pathway starting from mitochondrial ATP, through glycolysis and creatine phosphorylation, to satisfy the large energy demands of tumor cell division.

¹ Supported by Grant 6756 from the Association pour la Recherche sur le Cancer.

² To whom correspondence should be addressed, at LBSF IBCP UPR 412 CNRS, Passage du Vercors, F-69367 Lyon Cedex 07, France.

Received 1/31/92. Accepted 7/ 9/92.

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