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Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Mitochondrial Lipid Metabolism and Function Resulting in a Deficient Mitochondrial Bioenergetic Phenotype
Open accessAbstract
Previously, we identified a novel calcium-independent phospholipase, designated calcium-independent phospholipase A(2) gamma (iPLA(2)gamma), which possesses dual mitochondrial and peroxisomal subcellular localization signals. To identify the roles of iPLA(2)gamma in cellular bioenergetics, we generated mice null for the iPLA(2)gamma gene by eliminating the active site of the enzyme through homologous recombination. Mice null for iPLA(2)gamma display multiple bioenergetic dysfunctional phenotypes, including 1) growth retardation, 2) cold intolerance, 3) reduced exercise endurance, 4) greatly increased mortality from cardiac stress after transverse aortic constriction, 5) abnormal mitochondrial function with a 65% decrease in ascorbate-induced Complex IV-mediated oxygen consumption, and 6) a reduction in myocardial cardiolipin content accompanied by an altered cardiolipin molecular species composition. We conclude that iPLA(2)gamma is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition.
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Cites
Mitochondria: More Than Just a Powerhouse
McBride, H. M., Neuspiel, M., & Wasiak, S. (2006) · Current Biology · doi:10.1016/j.cub.2006.06.054 · Cited by 1,985
Leone, T. C., Lehman, J. J., Finck, B. N., Schaeffer, P. J., Wende, A. R., Boudina, S., Courtois, M., Wozniak, D. F., Sambandam, N., Bernal-Mizrachi, C., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030101 · Cited by 951
Lelliott, C. J., Medina-Gomez, G., Petrovic, N., Kis, A., Feldmann, H. M., Bjursell, M., Parker, N., Curtis, K., Campbell, M., Hu, P., et al. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040369 · Cited by 280
Sonoda, J., Mehl, I. R., Chong, L.-W., Nofsinger, R. R., & Evans, R. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611623104 · Cited by 266
Cited by
The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease
Long, J. Z., & Cravatt, B. F. (2011) · Chemical Reviews · doi:10.1021/cr200075y · Cited by 425
The complexity of cardiolipin in health and disease
Claypool, S. M., & Koehler, C. M. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.09.003 · Cited by 345
Schreiber, R., Diwoky, C., Schoiswohl, G., Feiler, U., Wongsiriroj, N., Abdellatif, M., Kolb, D., Hoeks, J., Kershaw, E. E., Sedej, S., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.004 · Cited by 322
The role of cardiolipin in the structural organization of mitochondrial membranes
Schlame, M., & Ren, M. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2009.04.019 · Cited by 248
Cardiolipin Remodeling in the Heart
Sparagna, G. C., & Lesnefsky, E. J. (2009) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e31819b5461 · Cited by 128
Metadata
- Authors
- Mancuso, D. J., Sims, H. F., Han, X., Jenkins, C. M., Guan, S. P., Yang, K., Moon, S. H., Pietka, T., Abumrad, N. A., Schlesinger, P. H., & Gross, R. W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 282
- Issue
- 48
- Pages
- 34611-34622
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2049018086
- Cited by
- 180
- References
- 4
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Mancuso, D. J., Sims, H. F., Han, X., Jenkins, C. M., Guan, S. P., Yang, K., Moon, S. H., Pietka, T., Abumrad, N. A., Schlesinger, P. H., & Gross, R. W. (2007). Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Mitochondrial Lipid Metabolism and Function Resulting in a Deficient Mitochondrial Bioenergetic Phenotype. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m707795200
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
