Abstract：
:The smallest rotary motor of living cells, F0F1-ATP synthase, couples proton flow-generated by the OXPHOS system-from the intermembrane space back to the matrix with the conversion of ADP to ATP. While all mutations affecting the multisubunit complexes of the OXPHOS system probably impact on the cell's output of ATP, only mutations in complex V can be considered to affect this output directly. So far, most of the F0F1-ATP synthase variations have been detected in the mitochondrial ATPase6 gene. In this study, the four most frequent mutations in the ATPase6 gene, namely L156R, L217R, L156P, and L217P, are studied for the first time together, both in primary cells and in cybrid clones. Arginine ("R") mutations were associated with a much more severe phenotype than Proline ("P") mutations, in terms of both biochemical activity and growth capacity. Also, a threshold effect in both "R" mutations appeared at 50% mutation load. Different mechanisms seemed to emerge for the two "R" mutations: the F1 seemed loosely bound to the membrane in the L156R mutant, whereas the L217R mutant induced low activity of complex V, possibly the result of a reduced rate of proton flow through the A6 channel.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Vazquez-Memije ME,Rizza T,Meschini MC,Nesti C,Santorelli FM,Carrozzo Rdoi
10.1002/jcb.22055subject
Has Abstractpub_date
2009-04-01 00:00:00pages
878-86issue
5eissn
0730-2312issn
1097-4644journal_volume
106pub_type
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