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Translational regulation of mitochondrial gene expression by nuclear genes of Saccharomyces cerevisiae
T D Fox1, M C Costanzo, C A Strick
1Section of Genetics and Development, Cornell University, Ithaca, New York 14853.
Abstract:
We describe several yeast nuclear mutations that specifically block expression of the mitochondrial genes encoding cytochrome c oxidase subunits II (COXII) and III (COXIII). These recessive mutations define positive regulators of mitochondrial gene expression that act at the level of translation. Mutations in the nuclear gene PET111 completely block accumulation of COXII, but the COXII mRNA is present in mutant cells at a level approximately one-third of that of the wild type. Mitochondrial suppressors of pet111 mutations correspond to deletions in mtDNA that result in fusions between the coxII structural gene and other mitochondrial genes. The chimeric mRNAs encoded by these fusions are translated in pet111 mutants; this translation leads to accumulation of functional COXII. The PET111 protein probably acts directly on coxII translation, because it is located in mitochondria. Translation of the mitochondrially coded mRNA for COXIII requires the action of at least three nuclear genes, PET494, PET54 and a newly discovered gene, provisionally termed PET55. Both the PET494 and PET54 proteins are located in mitochondria and therefore probably act directly on the mitochondrial translation system. Mutations in all three genes are suppressed in strains that contain chimeric coxIII mRNAs with the 5'-untranslated leaders of other mitochondrial transcripts fused to the coxIII coding sequence. The products of all three nuclear genes may form a complex and carry out a single function.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Researchers identified nuclear genes in yeast that regulate mitochondrial gene expression at the translation level. These genes are crucial for producing essential proteins for cytochrome c oxidase, vital for cellular respiration.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Mitochondrial gene expression is essential for cellular respiration.
- Cytochrome c oxidase subunits II (COXII) and III (COXIII) are critical components of the electron transport chain.
- Regulation of mitochondrial gene expression involves both nuclear and mitochondrial genomes.
Purpose of the Study:
- To identify and characterize nuclear genes regulating the translation of yeast mitochondrial genes COXII and COXIII.
- To elucidate the mechanisms by which nuclear-encoded proteins control mitochondrial gene expression.
Main Methods:
- Yeast genetics: isolation and characterization of nuclear mutations affecting mitochondrial gene expression.
- Molecular analysis: mRNA and protein level analysis in wild-type and mutant strains.
- Mitochondrial DNA manipulation: construction of chimeric mitochondrial genes to study suppression of mutations.
Main Results:
- Nuclear mutations in PET111, PET494, PET54, and PET55 specifically block translation of COXII and COXIII mRNAs.
- PET111 protein, located in mitochondria, directly regulates COXII translation.
- PET494, PET54, and PET55 proteins, also mitochondrial, are required for COXIII translation.
- Mitochondrial suppressors of pet111 mutations involve chimeric COXII mRNAs, indicating translation-dependent restoration of function.
- Chimeric COXIII mRNAs can suppress mutations in PET494, PET54, and PET55, suggesting a role for mRNA leaders in translation regulation.
Conclusions:
- Nuclear genes PET111, PET494, PET54, and PET55 encode positive regulators of mitochondrial translation for COXII and COXIII.
- These nuclear-encoded proteins likely act directly on the mitochondrial translation machinery.
- The findings highlight the intricate interplay between nuclear and mitochondrial genomes in regulating essential cellular functions.