Unremodeled and Remodeled Cardiolipin Are Functionally Indistinguishable in Yeast
| Autor: | Nathan N. Alder, Xianlin Han, J. Michael McCaffery, Erin N. Pryce, Murugappan Sathappa, Ya-Wen Lu, Kevin Whited, Matthew G. Baile, Steven M. Claypool |
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| Rok vydání: | 2014 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Cardiolipins Membrane lipids Saccharomyces cerevisiae Oxidative phosphorylation Mitochondrion Biology Biochemistry chemistry.chemical_compound Biosynthesis Membrane Biology Cardiolipin medicine Humans Molecular Biology Barth syndrome Cell Biology biology.organism_classification medicine.disease Mitochondria chemistry Barth Syndrome Membrane biogenesis lipids (amino acids peptides and proteins) Acyltransferases Gene Deletion Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 289:1768-1778 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m113.525733 |
| Popis: | After biosynthesis, an evolutionarily conserved acyl chain remodeling process generates a final highly homogeneous and yet tissue-specific molecular form of the mitochondrial lipid cardiolipin. Hence, cardiolipin molecules in different organisms, and even different tissues within the same organism, contain a distinct collection of attached acyl chains. This observation is the basis for the widely accepted paradigm that the acyl chain composition of cardiolipin is matched to the unique mitochondrial demands of a tissue. For this hypothesis to be correct, cardiolipin molecules with different acyl chain compositions should have distinct functional capacities, and cardiolipin that has been remodeled should promote cardiolipin-dependent mitochondrial processes better than its unremodeled form. However, functional disparities between different molecular forms of cardiolipin have never been established. Here, we interrogate this simple but crucial prediction utilizing the best available model to do so, Saccharomyces cerevisiae. Specifically, we compare the ability of unremodeled and remodeled cardiolipin, which differ markedly in their acyl chain composition, to support mitochondrial activities known to require cardiolipin. Surprisingly, defined changes in the acyl chain composition of cardiolipin do not alter either mitochondrial morphology or oxidative phosphorylation. Importantly, preventing cardiolipin remodeling initiation in yeast lacking TAZ1, an ortholog of the causative gene in Barth syndrome, ameliorates mitochondrial dysfunction. Thus, our data do not support the prevailing hypothesis that unremodeled cardiolipin is functionally distinct from remodeled cardiolipin, at least for the functions examined, suggesting alternative physiological roles for this conserved pathway. |
| Databáze: | OpenAIRE |
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