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Updated: May 29, 2026
08:35
Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
LRPPRC mutation suppresses cytochrome oxidase activity by altering mitochondrial RNA transcript stability in a mouse
Fenghao Xu1, Jane B L Addis, Jessie M Cameron
1Genetics and Genome Biology, The Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8.
The Biochemical Journal
|September 2, 2011
Summary
Leucine-rich pentatricopeptide repeat-containing (LRPPRC) protein is crucial for cytochrome c oxidase (COX) maturation by stabilizing mitochondrial DNA-encoded COX mRNA. Its absence leads to embryonic lethality in mice.
Area of Science:
- Mitochondrial biology
- Molecular genetics
- Biochemistry
Background:
- Cytochrome c oxidase (COX) is essential for cellular respiration.
- LRPPRC (leucine-rich pentatricopeptide repeat-containing) is implicated in COX maturation.
- Mitochondrial DNA (mtDNA) encodes key subunits of COX.
Purpose of the Study:
- To investigate the role of LRPPRC in COX maturation and mitochondrial gene expression.
- To identify the specific mechanism by which LRPPRC functions.
- To determine the binding site of LRPPRC on COX mRNA.
Main Methods:
- Generation of a mouse gene-trap model for LRPPRC.
- Biochemical analysis of mouse embryonic fibroblasts (MEFs) from mutant mice.
- In vitro binding assays using recombinant LRPPRC and COXI mRNA.
Main Results:
- Homozygous LRPPRC mutants exhibit embryonic lethality before 12.5 days post-coitum.
- Mutant MEFs show significantly reduced COX activity and impaired respiratory chain function.
- LRPPRC binds to a specific region of COXI mRNA, requiring the first 19 pentatricopeptide repeat motifs for full binding.
Conclusions:
- LRPPRC is essential for the maturation of cytochrome c oxidase.
- LRPPRC stabilizes mitochondrial mRNAs encoding COX subunits.
- The interaction between LRPPRC and COXI mRNA is critical for embryonic development.
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