Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Biol Cell. 2010 Jan 1;21(1):131-9. doi: 10.1091/mbc.E09-06-0483. Epub 2009 Nov 4.

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

Author information

1
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA.

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.

PMID:
19889836
PMCID:
PMC2801706
DOI:
10.1091/mbc.E09-06-0483
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center