Reference: Schlame M, et al. (2017)
Reference Help
Abstract
Tafazzin is a mitochondrial enzyme that transfers fatty acids from phospholipids to lysophospholipids. Mutations in tafazzin cause abnormal molecular species of cardiolipin and the clinical phenotype of Barth syndrome. However, the mechanism by which tafazzin creates acyl specificity has been controversial. We have shown that the lipid phase state can produce acyl specificity in the tafazzin reaction, but others have reported that tafazzin itself carries enzymatic specificity. To resolve this issue, we replicated and expanded the controversial experiments, i.e. the transfer of different acyl groups from phosphatidylcholine to monolysocardiolipin by yeast tafazzin. Our data show that this reaction requires the presence of detergent and does not take place in liposomes but in mixed micelles. To separate thermodynamic (lipid-dependent) from kinetic (enzyme-dependent) parameters, we followed the accumulation of cardiolipin during the reaction from the initial state to the equilibrium state. The transacylation rates of different acyl groups varied over 2 orders of magnitude and correlated tightly with the concentration of cardiolipin in the equilibrium state (lipid-dependent parameter). In contrast, the rates by which different transacylations approached the equilibrium state were very similar (enzyme-dependent parameter). Furthermore, we found that tafazzin catalyzes the remodeling of cardiolipin by combinations of forward and reverse transacylations, essentially creating an equilibrium distribution of acyl groups. These data strongly support the idea that the acyl specificity of the tafazzin reaction results from the physical properties of lipids.
- Reference Type
-
Journal Article
- Authors
-
Schlame M,
Xu Y,
Ren M
... Show all
Show fewer
- TAZ1
Gene Ontology Annotations
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page
scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header
to sort by that column; filter the table using the "Filter" box at the top of the table.
Evidence ID |
Analyze ID |
Gene/Complex |
Systematic Name/Complex Accession |
Qualifier |
Gene Ontology Term ID |
Gene Ontology Term |
Aspect |
Annotation Extension |
Evidence |
Method |
Source |
Assigned On |
Reference |
Phenotype Annotations
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page
scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header
to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i"
buttons located within a cell for an annotation to view further details.
Evidence ID |
Analyze ID |
Gene |
Gene Systematic Name |
Phenotype |
Experiment Type |
Experiment Type Category |
Mutant Information |
Strain Background |
Chemical |
Details |
Reference |
Disease Annotations
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page
scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header
to sort by that column; filter the table using the "Filter" box at the top of the table.
Evidence ID |
Analyze ID |
Gene |
Gene Systematic Name |
Disease Ontology Term |
Disease Ontology Term ID |
Qualifier |
Evidence |
Method |
Source |
Assigned On |
|
Reference |
Regulation Annotations
Increase the total number of rows displayed on this page using the pull-down located below the table, or use the
page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column
header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box
(for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to
further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, or SPELL.
Evidence ID |
Analyze ID |
Regulator |
Regulator Systematic Name |
Target |
Target Systematic Name |
Direction |
Regulation of |
Happens During |
Regulator Type |
Direction |
Regulation Of |
Happens During |
Method |
Evidence |
Strain Background |
Reference |
Post-translational Modifications
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the
page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to
sort by that column; filter the table using the "Filter" box at the top of the table.
|
|
|
|
Site |
|
Modification |
Modifier |
Source |
Reference |
Interaction Annotations
Genetic Interactions
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the
page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column
header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small
"i" buttons located within a cell for an annotation to view further details about experiment type and any other
genes involved in the interaction.
Evidence ID |
Analyze ID |
|
Interactor |
Interactor Systematic Name |
Interactor |
Interactor Systematic Name |
Allele |
Assay |
Annotation |
Action |
Phenotype |
SGA score |
P-value |
Source |
Reference |
Note |
Physical Interactions
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the
page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column
header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small
"i" buttons located within a cell for an annotation to view further details about experiment type and any other
genes involved in the interaction.
Evidence ID |
Analyze ID |
|
Interactor |
Interactor Systematic Name |
Interactor |
Interactor Systematic Name |
Assay |
Annotation |
Action |
Modification |
Source |
Reference |
Note |
Functional Complementation Annotations
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the
page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to
sort by that column; filter the table using the "Filter" box at the top of the table.
Complement ID |
Locus ID |
Gene |
Species |
Gene ID |
Strain background |
Direction |
Details |
Source |
Reference |