Deletion of mitochondrial ATPase inhibitor in the yeast Saccharomyces cerevisiae decreased cellular and mitochondrial ATP levels under non-nutritional conditions and induced a respiration-deficient cell-type

T-1, a mutant yeast lacking three regulatory proteins of F(1)F(o)ATPase, na mely ATPase inhibitor, 9K protein and 15K protein, grew on non-fermentable carbon source at the same rate as normal cells but was less viable when inc ubated in water. During the incubation, the cellular ATP content decreased rapidly in the T-1 cells but not in normal cells, and respiration-deficient cells appeared among the T-1 cells. The same mutation was also induced in D26 cells lacking only the ATPase inhibitor. Overexpression of the ATPase i nhibitor in YC63 cells, which were derived from the D26 strain harboring an expression vector containing the gene of the ATPase inhibitor, prevented t he decrease of cellular ATP level and the mutation. Isolated T-1 mitochondr ia exhibited ATP hydrolysis for maintenance of membrane potential when anti mycin A was added to the mitochondrial suspension, while normal and YC63 mi tochondria continued to show low hydrolytic activity and low membrane poten tial. Thus, it is likely that deletion of the ATPase inhibitor induces ATPa se activity of F(1)F(o)ATPase to create a dispensable membrane potential un der the non-nutritional conditions and that this depletes mitochondrial and cellular ATP. The depletion of mitochondrial ATP in turn leads to occurren ce of aberrant DNA in mitochondria.