Tight control of respiration by NADH dehydrogenase ND5 subunit gene expression in mouse mitochondria.
A mouse cell variant carrying in heteroplasmic form a nonsense mutation in the mitochondrial DNA-encoded ND5 subunit of the respiratory NADH dehydrogenase has been isolated and characterized. The derivation from this mutant of a large number of cell lines containing between 4 and 100% of the normal number of wild-type ND5 genes has allowed an analysis of the genetic and functional thresholds operating in mouse mitochondria. In wild-type cells, approximately 40% of the ND5 mRNA level was in excess of that required for ND5 subunit synthesis. However, in heteroplasmic cells, the functional mRNA level decreased in proportion to the number of wild-type ND5 genes over a 25-fold range, pointing to the lack of any compensatory increase in rate of transcription and/or stability of mRNA. Most strikingly, the highest ND5 synthesis rate was just sufficient to support the maximum NADH dehydrogenase-dependent respiration rate, with no upregulation of translation occurring with decreasing wild-type mRNA levels. These results indicate that, despite the large excess of genetic potential of the mammalian mitochondrial genome, respiration is tightly regulated by ND5 gene expression.
Bai
Y
Y
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Shakeley
R M
RM
Attardi
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D018388:Codon, Terminator; D004272:DNA, Mitochondrial / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D007700:Kinetics; D007739:L Cells; D046911:Macromolecular Substances; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D020125:Mutation, Missense; D009245:NADH Dehydrogenase / Q000235:genetics*; D010101:Oxygen Consumption; D017354:Point Mutation; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D018388:Codon, Terminator; D004272:DNA, Mitochondrial; D046911:Macromolecular Substances; D012333:RNA, Messenger; D009245:NADH Dehydrogenase