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, namely 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 incubated 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 inhibitor in YC63 cells, which were derived from the D26 strain harboring an expression vector containing the gene of the ATPase inhibitor, prevented the decrease of cellular ATP level and the mutation. Isolated T(1) mitochondria exhibited ATP hydrolysis for maintenance of membrane potential when antimycin A was added to the mitochondrial suspension, while normal and YC63 mitochondria continued to show low hydrolytic activity and low membrane potential. Thus, it is likely that deletion of the ATPase inhibitor induces ATPase activity of F(1)F(o)ATPase to create a dispensable membrane potential under the non-nutritional conditions and that this depletes mitochondrial and cellular ATP. The depletion of mitochondrial ATP in turn leads to occurrence of aberrant DNA in mitochondria.
Lu
Y M
YM
Department of Applied Chemistry, Muroran Institute of Technology, Muroran, Hokkaido 050-8585, Japan.
Miyazawa
K
K
Yamaguchi
K
K
Nowaki
K
K
Iwatsuki
H
H
Wakamatsu
Y
Y
Ichikawa
N
N
Hashimoto
T
T
D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D019069:Cell Respiration / Q000235:genetics; D004272:DNA, Mitochondrial / Q000502:physiology; D017353:Gene Deletion; D006868:Hydrolysis; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D000097795:ATPase Inhibitory Protein
D000255:Adenosine Triphosphate; D004272:DNA, Mitochondrial; D011506:Proteins; D006180:Proton-Translocating ATPases; D000097795:ATPase Inhibitory Protein