Role of Tafazzin in Mitochondrial Function, Development and Disease

Chin MT, Conway SJ.J Dev Biol. 2020 May 23;8(2):E10. doi: 10.3390/jdb8020010.PMID: 32456129 Review.



Tafazzin, an enzyme associated with the rare inherited x-linked disorder Barth Syndrome, is a nuclear encoded mitochondrial transacylase that is highly conserved across multiple species and plays an important role in mitochondrial function. Numerous studies have elucidated the mechanisms by which Tafazzin affects mitochondrial function, but its effects on development and susceptibility to adult disease are incompletely understood. The purpose of this review is to highlight previous functional studies across a variety of model organisms, introduce recent studies that show an important role in development, and also to provide an update on the role of Tafazzin in human disease. The profound effects of Tafazzin on cardiac development and adult cardiac homeostasis will be emphasized. These studies underscore the importance of mitochondrial function in cardiac development and disease, and also introduce the concept of Tafazzin as a potential therapeutic modality.


Figure 1 Biosynthesis of yeast cardiolipin (CL) within inner mitochondrial membrane. The initial steps of cardiolipin synthesis involve fatty acid esterification of glycerol-3-phosphate by glycerol-3-phosphate O-acyltransferase (GPAT) to generate phosphatidic acid (PA), which subsequently is modified by phosphatidate cytidylyltransferase 1 (CDS1) to form CDP-diacylglycerol (CDP-DAG). CDP-DAG then is modified by phosphatidylglycerolphosphate synthase (PGS1) to form phosphatidylglycerol phosphate (PGP), which is then modified by phosphatidylglycerophosphatase (GEP4) to phosphatidyl glycerol (PG). PG is then modified by cardiolipin synthase (CRD1) to form immature cardiolipin, which is then processed to MLCL by cardiolipin-specific deacylase 1 (CLD1). The yeast Tafazzin ortholog then reacylates MLCL to mature CL in mitochondria using a phosphatidylcholine acyl chain donor.