Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear mutant AB1-4A/8/100, a respiratory-competent strain altered in the regulation of ATP synthesis, has been shown to be modified in the relative stoichiometry of the mtDNA-encoded proteolipids of the F0 sector of ATP synthase: the ratios mutant/wild type of the proteolipids were equal to 0.4/0.7/1 for Su8/Su6/Su9, respectively. This defect results from the simultaneous presence of two nuclear genes which promote a cryosensitive phenotype on a nonfermentable carbon source. Measurements of mitochondrial protein synthesis carried out "in vivo" and "in organello" evidenced a specific defect in the synthesis of subunits 6 and 8. Measurements of the steady state levels of mitochondrial mRNA showed that the defect in subunits 6 and 8 was correlated with a modification of the expression of a cotranscript ATP8-ATP6. This cotranscript is matured at a unique site to give two cotranscripts of 4600 and 5200 bases in length. In mutant mitochondria, the ratio between both cotranscripts, 5200/4600, was lowered. In parallel, expression of the whole mitochondrial transcription unit supporting the genes COXI, ATP8, ATP6, and RF3 was enhanced. However, despite this over expression, the amount of the long cotranscript ATP8-ATP6 remained lower than in wild type mitochondria.
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PMID:Regulation by nuclear genes of the mitochondrial synthesis of subunits 6 and 8 of the ATP synthase of Saccharomyces cerevisiae. 153 Nov 41

Mitochondria translate the RNAs for 13 core polypeptides of respiratory chain and ATP synthase complexes that are essential for the assembly and function of these complexes. This process occurs in close proximity to the mitochondrial inner membrane. However, the mechanisms and molecular machinery involved in mitochondrial translation are not fully understood, and defects in this process can result in severe diseases. Stomatin-like protein (SLP)-2 is a mainly mitochondrial protein that forms cardiolipin- and prohibitin-enriched microdomains in the mitochondrial inner membrane that are important for the formation of respiratory supercomplexes and their function. Given this regulatory role of SLP-2 in processes closely associated with the mitochondrial inner membrane, we hypothesized that the function of SLP-2 would have an impact on mitochondrial translation. 35S-Methionine/cysteine pulse labeling of resting or activated T cells from T cell-specific Slp-2 knockout mice showed a significant impairment in the production of several mitochondrial DNA-encoded polypeptides following T cell activation, including Cytb, COXI, COXII, COXIII, and ATP6. Measurement of mitochondrial DNA stability and mitochondrial transcription revealed that this impairment was at the post-transcriptional level. Examination of mitochondrial ribosome assembly showed that SLP-2 migrated in sucrose-density gradients similarly to the large ribosomal subunit but that its deletion at the genetic level did not affect mitochondrial ribosome assembly. Functionally, the impairment in mitochondrial translation correlated with decreased interleukin-2 production in activated T cells. Altogether, these data show that SLP-2 acts as a general regulator of mitochondrial translation.
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PMID:Stomatin-like protein 2 deficiency results in impaired mitochondrial translation. 2865 2