DOI: 10.1073/pnas.0708959104. Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death

Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death

10.1073/pnas.0708959104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Polyphosphate (polyP) consists of tens to hundreds of phosphates, linked by ATP-like high-energy bonds. Although polyP is present in mammalian mitochondria, its physiological roles there are obscure. Here, we examine the involvement of polyP in mitochondrial energy metabolism and ion transport. We constructed a vector to express a mitochondrially targeted polyphosphatase, along with a GFP fluorescent tag. Specific reduction of mitochondrial polyP, by polyphosphatase expression, significantly modulates mitochondrial bioenergetics, as indicated by the reduction of inner membrane potential and increased NADH levels. Furthermore, reduction of polyP levels increases mitochondrial capacity to accumulate calcium and reduces the likelihood of the calcium-induced mitochondrial permeability transition, a central event in many types of necrotic cell death. This confers protection against cell death, including that induced by β-amyloid peptide, a pathogenic agent in Alzheimer's disease. These results demonstrate a crucial role played by polyP in mitochondrial function of mammalian cells.

Bibliography

Abramov, A. Y., Fraley, C., Diao, C. T., Winkfein, R., Colicos, M. A., Duchen, M. R., French, R. J., & Pavlov, E. (2007). Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death. Proceedings of the National Academy of Sciences, 104(46), 18091â18096.

Authors 8

Andrey Y. Abramov (first)
Cresson Fraley (additional)
Catherine T. Diao (additional)
Robert Winkfein (additional)
Michael A. Colicos (additional)
Michael R. Duchen (additional)
Robert J. French (additional)
Evgeny Pavlov (additional)

References 26 Referenced 195

Dates

Type	When
Created	17 years, 9 months ago (Nov. 6, 2007, 8:44 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:57 p.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 7:14 a.m.)
Issued	17 years, 9 months ago (Nov. 13, 2007)
Published	17 years, 9 months ago (Nov. 13, 2007)
Published Online	17 years, 9 months ago (Nov. 13, 2007)
Published Print	17 years, 9 months ago (Nov. 13, 2007)

Funders 0

None

BibTeX

@article{Abramov_2007, title={Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0708959104}, DOI={10.1073/pnas.0708959104}, number={46}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Abramov, Andrey Y. and Fraley, Cresson and Diao, Catherine T. and Winkfein, Robert and Colicos, Michael A. and Duchen, Michael R. and French, Robert J. and Pavlov, Evgeny}, year={2007}, month=nov, pages={18091–18096} }

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