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Novel role of ATPase subunit C targeting peptides beyond mitochondrial protein import.

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dc.contributor.author Vives-Bauzà, Cristòfol
dc.contributor.author Magrané, Jordi
dc.contributor.author Andreu, Antonio L.
dc.contributor.author Manfredi, Giovanni
dc.date.accessioned 2018-10-04T11:02:07Z
dc.identifier.uri http://hdl.handle.net/11201/147926
dc.description.abstract In mammals, subunit c of the F(1)F(0)-ATP synthase has three isoforms (P1, P2, and P3). These isoforms differ by their cleavable mitochondrial targeting peptides, whereas the mature peptides are identical. To investigate this apparent genetic redundancy, we knocked down each of the three subunit c isoform by RNA interference in HeLa cells. Silencing any of the subunit c isoforms individually resulted in an ATP synthesis defect, indicating that these isoforms are not functionally redundant. We found that subunit c knockdown impaired the structure and function of the mitochondrial respiratory chain. In particular, P2 silencing caused defective cytochrome oxidase assembly and function. Because the expression of exogenous P1 or P2 was able to rescue the respective silencing phenotypes, but the two isoforms were unable to cross-complement, we hypothesized that their functional specificity resided in their targeting peptides. In fact, the expression of P1 and P2 targeting peptides fused to GFP variants rescued the ATP synthesis and respiratory chain defects in the silenced cells. Our results demonstrate that the subunit c isoforms are nonredundant, because they differ functionally by their targeting peptides, which, in addition to mediating mitochondrial protein import, play a yet undiscovered role in respiratory chain maintenance.
dc.format application/pdf
dc.relation.isformatof Reproducció del document publicat a: https://doi.org/10.1091/mbc.E09-06-0483
dc.relation.ispartof Molecular Biology of the Cell, 2010, vol. 21, num. 1, p. 131-139
dc.rights cc-by-nc-sa (c) Vives-Bauza, ristòfolC et al., 2010
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/es
dc.subject.classification 616.8 - Neurologia. Neuropatologia. Sistema nerviós
dc.subject.other 616.8 - Neurology. Neuropathology. Nervous system
dc.title Novel role of ATPase subunit C targeting peptides beyond mitochondrial protein import.
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2018-10-04T11:02:07Z
dc.date.embargoEndDate info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.identifier.doi https://doi.org/10.1091/mbc.E09-06-0483


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cc-by-nc-sa (c) Vives-Bauza, ristòfolC et al., 2010 Except where otherwise noted, this item's license is described as cc-by-nc-sa (c) Vives-Bauza, ristòfolC et al., 2010

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