New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome.

New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. Research Abstract Details 

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New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. Abstract Text:

Guiling Li,Shuliang Chen,Morgan N Thompson,Miriam L Greenberg,

Recent studies have revealed an array of novel regulatory mechanisms involved in the biosynthesis and metabolism of the phospholipid cardiolipin (CL), the signature lipid of mitochondria. CL plays an important role in cellular and mitochondrial function due in part to its association with a large number of mitochondrial proteins, including many which are unable to function optimally in the absence of CL. New insights into the complexity of regulation of CL provide further evidence of its importance in mitochondrial and cellular function. The biosynthesis of CL in yeast occurs via three enzymatic steps localized in the mitochondrial inner membrane. Regulation of this process by general phospholipid cross-pathway control and factors affecting mitochondrial development has been previously established. In this review, novel regulatory mechanisms that control CL biosynthesis are discussed. A unique form of inositol-mediated regulation has been identified in the CL biosynthetic pathway, independent of the INO2-INO4-OPI1 regulatory circuit that controls general phospholipid biosynthesis. Inositol leads to decreased activity of phosphatidylglycerolphosphate (PGP) synthase, which catalyzes the committed step of CL synthesis. Reduced enzymatic activity does not result from alteration of expression of the structural gene, but is instead due to increased phosphorylation of the enzyme. This is the first demonstration of phosphorylation in response to inositol and may have significant implications in understanding the role of inositol in other cellular regulatory pathways. Additionally, synthesis of CL has been shown to be dependent on mitochondrial pH, coordinately controlled with synthesis of mitochondrial phosphatidylethanolamine (PE), and may be regulated by mitochondrial DNA absence sensitive factor (MIDAS). Further characterization of these regulatory mechanisms holds great potential for the identification of novel functions of CL in mitochondrial and cellular processes.

New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. Publishing Authors By Initials

G Li,S Chen,MN Thompson,ML Greenberg,

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New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. Journal Published:

PUBLICATION TYPE: Review

Journal: Biochimica et biophysica acta

VOLUME: 1771

Page Numbers: 432-41

Journal Abbreviation: Biochim. Biophys. Acta

ISSN: 0006-3002

DAY: 8

MONTH: 07

YEAR: 2006

New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. Information

Number of References: 118

LANGUAGE: eng

NlmUniqueID: 217513

New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. Keywords Mesh Terms:

KEYWORDS: Transferases (Other Substituted Phosphat

MESH TERMS: metabolism

Chemical & Substance for Abstract: New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome. Information

Substance Name: PGS1 protein, S cerevisiae

Registry Number: EC 2.7.8.8

Grant and Affiliation Information for New insights into the regulation of cardiolipin biosynthesis in yeast: implications for Barth syndrome.

AFFILIATION: Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA.

Country: Netherlands

AGENCY: United States NHLBI

GRANT: HL 62263

ACRONYM: HL

MEDLINETA: Biochim Biophys Acta

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