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The Role of Cardiolipin in Cardiovascular Health.

Shen Z, Ye C, McCain K, Greenberg ML - Biomed Res Int (2015)

Bottom Line: Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria.The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways.In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.

ABSTRACT
Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the gene encoding tafazzin, the transacylase that carries out the second CL remodeling step. In addition to BTHS, CL is linked to other cardiovascular diseases (CVDs), including cardiomyopathy, atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and Tangier disease. The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways. In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health.

No MeSH data available.


Related in: MedlinePlus

Cardiolipin synthesis and remodeling pathway in humans and yeast. Phosphatidic acid (PA) is converted to CDP-diacylglycerol (CDP-DAG) by CDP-DAG synthase. Phosphatidylglycerolphosphate synthase catalyzes the conversion of CDP-DAG to phosphatidylglycerolphosphate (PGP), which is dephosphorylated to phosphatidylglycerol (PG). PG is converted to unremodeled CL with mostly saturated acyl chains (CLSAT). CLSAT is deacylated to monolyso-CL (MLCL) by phospholipases and MLCL is reacylated to CL with mostly unsaturated acyl chains (CLUNSAT). The genes encoding human enzymes are indicated in red, and genes that encode yeast enzymes are in blue.
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fig1: Cardiolipin synthesis and remodeling pathway in humans and yeast. Phosphatidic acid (PA) is converted to CDP-diacylglycerol (CDP-DAG) by CDP-DAG synthase. Phosphatidylglycerolphosphate synthase catalyzes the conversion of CDP-DAG to phosphatidylglycerolphosphate (PGP), which is dephosphorylated to phosphatidylglycerol (PG). PG is converted to unremodeled CL with mostly saturated acyl chains (CLSAT). CLSAT is deacylated to monolyso-CL (MLCL) by phospholipases and MLCL is reacylated to CL with mostly unsaturated acyl chains (CLUNSAT). The genes encoding human enzymes are indicated in red, and genes that encode yeast enzymes are in blue.

Mentions: Unlike mitochondrial membrane lipids that are synthesized in the endoplasmic reticulum, de novo synthesis of CL occurs exclusively in the inner membrane of the mitochondria [9], in a series of well-characterized steps that are highly conserved from yeast to higher eukaryotes [10]. As shown in Figure 1, the first step in the CL biosynthetic pathway is the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), which is catalyzed in the inner membrane by CDP-DAG synthase encoded by TAM41 [11–13] in yeast. PGS1 encoded phosphatidylglycerolphosphate synthase catalyzes transfer of the phosphatidyl group from CDP-DAG to a glycerol-3-phosphate molecule to generate phosphatidylglycerolphosphate (PGP) [14, 15]. PGP is subsequently dephosphorylated to phosphatidylglycerol (PG) by PGP phosphatase [16, 17], encoded by PTPMT1 in mammals [18, 19] and GEP4 in yeast [20]. The final step in the biosynthetic pathway is carried out by CL synthase, encoded by hCLS1 in human cells [21–23] and by CRD1 in yeast [24–26]. In this step, a second phosphatidyl group is added to PG from another CDP-DAG molecule, generating unremodeled CL [9, 23, 27].


The Role of Cardiolipin in Cardiovascular Health.

Shen Z, Ye C, McCain K, Greenberg ML - Biomed Res Int (2015)

Cardiolipin synthesis and remodeling pathway in humans and yeast. Phosphatidic acid (PA) is converted to CDP-diacylglycerol (CDP-DAG) by CDP-DAG synthase. Phosphatidylglycerolphosphate synthase catalyzes the conversion of CDP-DAG to phosphatidylglycerolphosphate (PGP), which is dephosphorylated to phosphatidylglycerol (PG). PG is converted to unremodeled CL with mostly saturated acyl chains (CLSAT). CLSAT is deacylated to monolyso-CL (MLCL) by phospholipases and MLCL is reacylated to CL with mostly unsaturated acyl chains (CLUNSAT). The genes encoding human enzymes are indicated in red, and genes that encode yeast enzymes are in blue.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig1: Cardiolipin synthesis and remodeling pathway in humans and yeast. Phosphatidic acid (PA) is converted to CDP-diacylglycerol (CDP-DAG) by CDP-DAG synthase. Phosphatidylglycerolphosphate synthase catalyzes the conversion of CDP-DAG to phosphatidylglycerolphosphate (PGP), which is dephosphorylated to phosphatidylglycerol (PG). PG is converted to unremodeled CL with mostly saturated acyl chains (CLSAT). CLSAT is deacylated to monolyso-CL (MLCL) by phospholipases and MLCL is reacylated to CL with mostly unsaturated acyl chains (CLUNSAT). The genes encoding human enzymes are indicated in red, and genes that encode yeast enzymes are in blue.
Mentions: Unlike mitochondrial membrane lipids that are synthesized in the endoplasmic reticulum, de novo synthesis of CL occurs exclusively in the inner membrane of the mitochondria [9], in a series of well-characterized steps that are highly conserved from yeast to higher eukaryotes [10]. As shown in Figure 1, the first step in the CL biosynthetic pathway is the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), which is catalyzed in the inner membrane by CDP-DAG synthase encoded by TAM41 [11–13] in yeast. PGS1 encoded phosphatidylglycerolphosphate synthase catalyzes transfer of the phosphatidyl group from CDP-DAG to a glycerol-3-phosphate molecule to generate phosphatidylglycerolphosphate (PGP) [14, 15]. PGP is subsequently dephosphorylated to phosphatidylglycerol (PG) by PGP phosphatase [16, 17], encoded by PTPMT1 in mammals [18, 19] and GEP4 in yeast [20]. The final step in the biosynthetic pathway is carried out by CL synthase, encoded by hCLS1 in human cells [21–23] and by CRD1 in yeast [24–26]. In this step, a second phosphatidyl group is added to PG from another CDP-DAG molecule, generating unremodeled CL [9, 23, 27].

Bottom Line: Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria.The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways.In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.

ABSTRACT
Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the gene encoding tafazzin, the transacylase that carries out the second CL remodeling step. In addition to BTHS, CL is linked to other cardiovascular diseases (CVDs), including cardiomyopathy, atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and Tangier disease. The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways. In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health.

No MeSH data available.


Related in: MedlinePlus