Unremodeled and Remodeled Cardiolipin Are Functionally Indistinguishable in Yeast

Baile, Matthew G.; Sathappa, Murugappan; Lu, Ya Wen; Pryce, Erin N.; Whited, Kevin; McCaffery, J. Michael; Han, Xianlin; Alder, Nathan N.; Claypool, Steven M.

doi:10.1074/jbc.m113.525733

Cited by 103 publications

(171 citation statements)

References 76 publications

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“…In Saccharomyces cerevisiae lacking tafazzin, an additional deletion of the CL-specifi c phospholipase, Cld1, prevents the accumulation of MLCL, inhibits CL remodeling, and rescues the mitochondrial respiratory defect, strongly suggesting that the respiratory defect had been due to the accumulation of MLCL and/or the decrease in the total content of CL ( 25 ). In mammalian cells, two additional enzymes, lysocardiolipin acyltransferase 1 (AL-CAT1) and MLCL acyltransferase 1 (MLCL AT-1), can use acyl-CoAs to esterify MLCL ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…In Acsl1 T Ϫ / Ϫ hearts, normalizing the amount of linoleate present in CL did not improve respiratory dysfunction. Similarly, in S. cerevisiae , CL remodeling can be inhibited without impairing basal or ADP-stimulated mitochondrial O 2 consumption ( 25,26 ). Thus, in both yeast and in Acsl1…”

Section: Acsl1 Activates Linoleate For Cardiolipin Remodelingmentioning

confidence: 99%

“…The relevance of CL acyl-chain composition to normal oxidative phosphorylation is controversial ( 25,26 ). In order to determine whether the impaired respiratory function of mitochondria from Acsl1 T Ϫ / Ϫ hearts resulted from the presence of linoleate-defi cient mitochondrial CL, we fed control and Acsl1 T Ϫ / Ϫ mice a high saffl ower oil diet, in which 75% of the fatty acids are linoleate.…”

Section: Dietary Linoleate Enrichment Normalized Tetralinoleoyl-cl Comentioning

confidence: 99%

“…H9c2 cells were cultured to confl uence in 25 measurements, 0.4 ml media was collected in a tube containing 20 µL 15% BSA and then incubated with 100 µL 20% perchloric acid overnight at 4°C. The acidifi ed media was centrifuged at 20,000 rpm for 5 min, and radioactivity in the supernatant was counted to determine acid-soluble metabolites (ASMs).…”

Section: Cellular Phospholipid Incorporationmentioning

confidence: 99%

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Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function

Grevengoed

Martin

Katunga

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.orgIn order to metabolize long-chain fatty acids in pathways of ␤ -oxidation or the synthesis of complex lipids, they must fi rst be activated to acyl-CoAs by long-chain acyl-CoA synthetases (ACSLs). The fi ve mammalian ACSL isoforms each have a specifi c substrate preference, subcellular location, and tissue distribution ( 1 ). In the heart, the ACSL1 isoform predominates, such that with defi ciency, total ACSL specifi c activity and fatty acid oxidation decrease by more than 90% ( 2 ). Because ACSL activity is required for the incorporation of fatty acids into phospholipids, we asked whether the ACSL1 isoform is also required for the synthesis and remodeling of cardiac phospholipids, particularly cardiolipin (CL).The mitochondrial phospholipid CL contributes to many aspects of mitochondrial function, including energy production through oxidative phosphorylation ( 3, 4 ), mitochondrial fi ssion and fusion ( 5, 6 ), and cellular apoptosis ( 7 ). Tetralinoleoyl-CL is the predominant CL species in the mammalian heart ( 8 ), but the mechanism by which this species is formed is unclear. Because the enzymes of CL synthesis lack acyl-chain specifi city, nascent CL contains a mixture of acyl chain lengths and degrees of unsaturation ( 9 ). To obtain mature CL, most remodeling occurs within the mitochondria by sequentially removing each acyl chain to form monolyso-CL (MLCL) and then replacing the missing fatty acid with linoleate (18:2). Linoleate is added by transacylation from a donor phospholipid ( 10 ) or by direct esterifi cation of a linoleoyl-CoA ( 11, 12 ).The transacylase tafazzin is believed to be responsible for cardiolipin remodeling. Mutations in tafazzin cause Barth syndrome, an X-linked cardiomyopathy characterized by skeletal muscle weakness and heart failure in Abstract Long-chain acyl-CoA synthetase 1 (ACSL1) contributes more than 90% of total cardiac ACSL activity, but its role in phospholipid synthesis has not been determined. Mice with an inducible knockout of ACSL1 ( Acsl1 T ؊ / ؊ ) have impaired cardiac fatty acid oxidation and rely on glucose for ATP production. Because ACSL1 exhibited a strong substrate preference for linoleate, we investigated the composition of heart phospholipids.

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Section: Discussionmentioning

confidence: 99%

Section: Acsl1 Activates Linoleate For Cardiolipin Remodelingmentioning

confidence: 99%

Section: Dietary Linoleate Enrichment Normalized Tetralinoleoyl-cl Comentioning

confidence: 99%

Section: Cellular Phospholipid Incorporationmentioning

confidence: 99%

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Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function

Grevengoed

Martin

Katunga

et al. 2015

Journal of Lipid Research

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“…To assess the function of the assorted Psd1p constructs and mutants, overnight cultures grown in synthetic complete dextrose (SCD; 0.17% yeast nitrogen base, 0.5% ammonium sulfate, 0.2% complete amino acid mixture, 2% dextrose) supplemented with 2 mM ethanolamine were spotted on synthetic complete dextrose plates in the absence or presence of 2 mM ethanolamine, as indicated. Deletion strains were generated by PCR-mediated gene replacement of the entire open reading frame as previously described (32,33).…”

Section: Methodsmentioning

confidence: 99%

Phosphatidylserine Decarboxylase 1 Autocatalysis and Function Does Not Require a Mitochondrial-specific Factor

Onguka¹,

Calzada²,

Ogunbona³

et al. 2015

Journal of Biological Chemistry

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Background: Autocatalytic processing is required for Psd1p function. Molecular requirements for Psd1p autocatalysis are largely undefined. Results: Psd1p autocatalysis occurs in yeast mutants lacking its substrate or mitochondrial-specific lipids. Furthermore, Psd1p re-directed to the endoplasmic reticulum undergoes autocatalysis and is functional in vivo. Conclusion: Psd1p autocatalysis does not require its substrate or mitochondrial-specific lipids, proteins, or co-factors. Significance: Once membrane-embedded, Psd1p is autocatalytically self-sufficient.

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The role of nonbilayer phospholipids in mitochondrial structure and function

2017

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Edited by Wilhelm JustMitochondrial structure and function are influenced by the unique phospholipid composition of its membranes. While mitochondria contain all the major classes of phospholipids, recent studies have highlighted specific roles of the nonbilayer-forming phospholipids phosphatidylethanolamine (PE) and cardiolipin (CL) in the assembly and activity of mitochondrial respiratory chain (MRC) complexes. The nonbilayer phospholipids are cone-shaped molecules that introduce curvature stress in the bilayer membrane and have been shown to impact mitochondrial fusion and fission. In addition to their overlapping roles in these mitochondrial processes, each nonbilayer phospholipid also plays a unique role in mitochondrial function; for example, CL is specifically required for MRC supercomplex formation. Recent discoveries of mitochondrial PE-and CL-trafficking proteins and prior knowledge of their biosynthetic pathways have provided targets for precisely manipulating nonbilayer phospholipid levels in the mitochondrial membranes in vivo. Thus, the genetic mutants of these pathways could be valuable tools in illuminating molecular functions and biophysical properties of nonbilayer phospholipids in driving mitochondrial bioenergetics and dynamics.

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Unremodeled and Remodeled Cardiolipin Are Functionally Indistinguishable in Yeast

Cited by 103 publications

References 76 publications

Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function

Acyl-CoA synthetase 1 deficiency alters cardiolipin species and impairs mitochondrial function

Phosphatidylserine Decarboxylase 1 Autocatalysis and Function Does Not Require a Mitochondrial-specific Factor

The role of nonbilayer phospholipids in mitochondrial structure and function

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