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Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import
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 i...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801706/ https://www.ncbi.nlm.nih.gov/pubmed/19889836 http://dx.doi.org/10.1091/mbc.E09-06-0483 |
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author | Vives-Bauza, Cristofol Magrané, Jordi Andreu, Antoni L. Manfredi, Giovanni |
author_facet | Vives-Bauza, Cristofol Magrané, Jordi Andreu, Antoni L. Manfredi, Giovanni |
author_sort | Vives-Bauza, Cristofol |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2801706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-28017062010-03-16 Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import Vives-Bauza, Cristofol Magrané, Jordi Andreu, Antoni L. Manfredi, Giovanni Mol Biol Cell Articles 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. The American Society for Cell Biology 2010-01-01 /pmc/articles/PMC2801706/ /pubmed/19889836 http://dx.doi.org/10.1091/mbc.E09-06-0483 Text en © 2010 by The American Society for Cell Biology |
spellingShingle | Articles Vives-Bauza, Cristofol Magrané, Jordi Andreu, Antoni L. Manfredi, Giovanni Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import |
title | Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import |
title_full | Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import |
title_fullStr | Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import |
title_full_unstemmed | Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import |
title_short | Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import |
title_sort | novel role of atpase subunit c targeting peptides beyond mitochondrial protein import |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801706/ https://www.ncbi.nlm.nih.gov/pubmed/19889836 http://dx.doi.org/10.1091/mbc.E09-06-0483 |
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