Disruption of a mitochondrial RNA-binding protein gene results in decreased cytochrome b expression and a marked reduction in ubiquinol-cytochrome c reductase activity in mouse heart mitochondria.
Mice homozygous for a defect in the PTCD2 (pentatricopeptide repeat domain protein 2) gene were generated in order to study the role of this protein in mitochondrial RNA metabolism. These mice displayed specific but variable reduction of ubiquinol-cytochrome c reductase complex activity in mitochondria of heart, liver and skeletal muscle due to a decrease in the expression of mitochondrial DNA-encoded cytochrome b, the catalytic core of the complex. This reduction in mitochondrial function has a profound effect on the myocardium, with replacement of ventricular cardiomyocytes by fibro-fatty tissue. Northern blotting showed a reduction in the mRNA for the mitochondrial DNA encoded proteins cytochrome b (cytb) and ND5 (NADH dehydrogenase subunit 5) and an elevation in a combined pre-processed ND5-CYTB transcript. This suggests that the PTCD2 protein is involved in processing RNA transcripts involving cytochrome b derived from mitochondrial DNA. This defines the site for PTCD2 action in mammalian mitochondria and suggests a possible role for dysfunction of this protein in the aetiology of heart failure.
Xu
Fenghao
F
Programme in Genetics and Genome Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Ackerley
Cameron
C
Maj
Mary C
MC
Addis
Jane B L
JB
Levandovskiy
Valeriy
V
Lee
Jisoo
J
Mackay
Nevena
N
Cameron
Jessie M
JM
Robinson
Brian H
BH
D000818:Animals; D045303:Cytochromes b / Q000096:biosynthesis*; D014450:Electron Transport Complex III / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D050259:Genes, Mitochondrial / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000502:physiology; D012313:RNA / Q000378:metabolism; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology
D024101:Mitochondrial Proteins; C532970:PTCD2 protein, mouse; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins; D012313:RNA; D045303:Cytochromes b; D014450:Electron Transport Complex III