![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on November 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 29, 2002
Revised on July 29, 2002
Accepted on August 19, 2002
1 Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY
2 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX
3 Departments of Neurology and of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, NY
* Corresponding author. E-mail address: eas3{at}columbia.edu.
Unlike most organisms, the mtDNA of Chlamydomonas reinhardtii, a green alga, does not encode subunit 6 of FF1-ATP synthase. We hypothesized that C. reinhardtii ATPase 6 is nucleus-encoded, and identified cDNAs and a single-copy nuclear gene specifying this subunit (CrATP6, with 8 exons, 4 of which encode a mitochondrial targeting signal [MTS]). Although the algal and human ATP6 genes are in different subcellular compartments and the encoded polypeptides are highly diverged, their secondary structures are remarkably similar. When CrATP6 was expressed in human cells, a significant amount of the precursor polypeptide was targeted to mitochondria, the MTS was cleaved within the organelle, and the mature polypeptide was assembled into human ATP synthase. In spite of the evolutionary distance between algae and mammals, C. reinhardtii ATPase 6 functioned in human cells, as deficiencies in both cell viability and ATP synthesis in transmitochondrial cell lines harboring a pathogenic mutation in the human mtDNA-encoded ATP6 gene were overcome by expression of CrATP6. The ability to express a nucleus-encoded version of a mammalian mtDNA-encoded protein may provide a way to import other highly hydrophobic proteins into mitochondria, and could serve as the basis for a gene therapy approach to treat human mitochondrial diseases.
This article has been cited by other articles:
|
|
 |
|
  X. Qi, L. Sun, A. S. Lewin, W. W. Hauswirth, and J. Guy The Mutant Human ND4 Subunit of Complex I Induces Optic Neuropathy in the Mouse Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mattiazzi, C. Vijayvergiya, C. D. Gajewski, D. C. DeVivo, G. Lenaz, M. Wiedmann, and G. Manfredi The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants Hum. Mol. Genet., April 15, 2004; 13(8): 869 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Oca-Cossio, L. Kenyon, H. Hao, and C. T. Moraes Limitations of Allotopic Expression of Mitochondrial Genes in Mammalian Cells Genetics, October 1, 2003; 165(2): 707 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. DiMauro and E. A. Schon Mitochondrial Respiratory-Chain Diseases N. Engl. J. Med., June 26, 2003; 348(26): 2656 - 2668. [Full Text] [PDF]
|
|
