The Amyloid-[beta]-SDR5C1(ABAD) Interaction Does Not Mediate a Specific Inhibition of Mitochondrial RNase P

The Amyloid-[beta]-SDR5C1(ABAD) Interaction Does Not Mediate a Specific Inhibition of Mitochondrial RNase P

The amyloid-[beta] peptide (A[beta]) is suggested to cause mitochondrial dysfunction in Alzheimer's disease. The mitochondrial dehydrogenase SDR5C1 (also known as ABAD) was shown to bind A[beta] and was proposed to thereby mediate mitochondrial toxicity, but the molecular mechanism has not been...

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Bibliographic Details
Published in:PloS one 2013-06, Vol.8 (6), p.e65609
Main Authors: Vilardo, Elisa, Rossmanith, Walter
Format: Article
Language:eng
Subjects:
Alzheimer's disease
Methylation
Peptides
Ribonuclease
Transfer RNA
Transferases
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Summary:The amyloid-[beta] peptide (A[beta]) is suggested to cause mitochondrial dysfunction in Alzheimer's disease. The mitochondrial dehydrogenase SDR5C1 (also known as ABAD) was shown to bind A[beta] and was proposed to thereby mediate mitochondrial toxicity, but the molecular mechanism has not been clarified. We recently identified SDR5C1 as an essential component of human mitochondrial RNase P and its associated tRNA:m.sup.1 R9 methyltransferase, the enzymes responsible for tRNA 5'-end processing and methylation of purines at tRNA position 9, respectively. With this work we investigated whether SDR5C1's role as a subunit of these two tRNA-maturation activities represents the mechanistic link between A[beta] and mitochondrial dysfunction. Using recombinant enzyme components, we tested RNase P and methyltransferase activity upon titration of A[beta]. Micromolar concentrations of monomeric or oligomerized A[beta] were required to inhibit tRNA 5'-end processing and position 9 methylation catalyzed by the SDR5C1-containing enzymes, yet similar concentrations of A[beta] also inhibited related RNase P and methyltransferase activities, which do not contain an SDR5C1 homolog. In conclusion, the proposed deleterious effect of A[beta] on mitochondrial function cannot be explained by a specific inhibition of mitochondrial RNase P or its tRNA:m.sup.1 R9 methyltransferase subcomplex, and the molecular mechanism of SDR5C1-mediated A[beta] toxicity remains unclear.
ISSN:1932-6203
1932-6203