Reduction of nuclear encoded enzymes of mitochondrial energy metabolism in cells devoid of mitochondrial DNA.
Mitochondrial DNA (mtDNA) depletion syndromes are generally associated with reduced activities of oxidative phosphorylation (OXPHOS) enzymes that contain subunits encoded by mtDNA. Conversely, entirely nuclear encoded mitochondrial enzymes in these syndromes, such as the tricarboxylic acid cycle enzyme citrate synthase (CS) and OXPHOS complex II, usually exhibit normal or compensatory enhanced activities. Here we report that a human cell line devoid of mtDNA (HEK293 ρ(0) cells) has diminished activities of both complex II and CS. This finding indicates the existence of a feedback mechanism in ρ(0) cells that downregulates the expression of entirely nuclear encoded components of mitochondrial energy metabolism.
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Salzburg, Austria. ed.mueller@salk.at
Edith E
EE
Mueller
Johannes A
JA
Mayr
Franz A
FA
Zimmermann
René G
RG
Feichtinger
Olaf
O
Stanger
Wolfgang
W
Sperl
Barbara
B
Kofler
D002467:Cell Nucleus / Q000201:enzymology*; D002950:Citrate (si)-Synthase / Q000172:deficiency*; D004272:DNA, Mitochondrial; D042963:Electron Transport Complex II / Q000172:deficiency*; D004734:Energy Metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D014157:Transcription Factors / Q000235:genetics
D004272:DNA, Mitochondrial; D014157:Transcription Factors; D042963:Electron Transport Complex II; D002950:Citrate (si)-Synthase