The Role of Cardiolipin in Cardiovascular Health

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.

Figure 1

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 (CL_SAT). CL_SAT is deacylated to monolyso-CL (MLCL) by phospholipases and MLCL is reacylated to CL with mostly unsaturated acyl chains (CL_UNSAT). The genes encoding human enzymes are indicated in red, and genes that encode yeast enzymes are in blue.