The Enzymatic Function of Tafazzin

Abstract

Tafazzin is a putative enzyme that is involved in cardiolipin metabolism, it may carry mutations responsible for Barth syndrome. To identify the biochemical reaction catalyzed by tafazzin, we expressed the full-length isoform of Drosophila melanogaster tafazzin in a baculovirus-Sf9 insect cell system. Tafazzin expression induced a new enzymatic function in Sf9 cell mitochondria, namely 1-palmitoyl-2-[ 14 C]linoleoyl-phosphatidylcholine:monolysocardiolipin linoleoyltransferase. We also found evidence for the reverse reaction, because tafazzin expression caused transfer of acyl groups from phospholipids to 1-[ 14 C]palmitoyl-2-lyso-phosphatidylcholine. An affinity-purified tafazzin construct, tagged with the maltose-binding protein, catalyzed both forward and reverse transacylations between cardiolipin and phosphatidylcholine, but was unable to utilize CoA or acyl-CoA as substrates. Whereas tafazzin supported transacylations between various phospholipid-lysophospholipid pairs, it showed the highest rate for the phosphatidylcholine-cardiolipin transacylation. Transacylation activities were about 10-fold higher for linoleoyl groups than for oleoyl groups, and they were negligible for arachidonoyl groups. The data show that Drosophila tafazzin is a CoA-independent, acylspecific phospholipid transacylase with substrate preference for cardiolipin and phosphatidylcholine.

Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

“…For example, a similar broad distribution of cardiolipin molecular species was observed between day 5 and 15 for normal mouse cardiac development (data not shown) as well as in mature mouse brain ( 16,26 ). It is interesting that this broad distribution of cardiolipin molecular species is also observed in various disease states, culture conditions, and transgenic models of enzymes that catalyze cardiolipin remodeling ( 23,(41)(42)(43)(44)(45). This suggests a common remodeling event or role of various acyltransferases, transacylases, or phospholipases involved in this stage of the remodeling process.…”

“…CL, cardiolipin. is commonly believed that acyl CoA as well as PC and PE contribute to the pool of acyl chains used for cardiolipin remodeling in mitochondria ( 20,21,23,24,38,43 ). In addition, Lands cycle remodeling utilizes the sn -2 positions of glycerophospholipids for remodeling ( 49,50 ).…”

“…The newly formed polyglycerophospholipid is referred to as immature cardiolipin, which is then deacylated and extensively remodeled using acyltransferase(s) and/or transacylase(s) ( 21,22 ). Cardiolipin remodeling utilizes acyl CoA and acyl chains from the sn -2 position of choline glycerophospholipids (PC ) and ethanolamine glycerophospholipids (PE) accordingly as acyl donors ( 20,23,24 ). The balance of acyltransferase and transacylase activities as well as acyl chain selectivities is refl ected in the acyl chain pool, which sculpts nascent cardiolipins into mature cardiolipin molecular species.…”

The Cardiolipin Transacylase, Tafazzin, Associates with Two Distinct Respiratory Components Providing Insight into Barth Syndrome

“…Taz1p is a phospholipid transacylase that can utilize MLCL as acyl chain acceptor (Xu et al, 2006b) and localizes to both the IM and OM, always facing the IMS (Claypool et al, 2006). Therefore, we wanted to determine the importance of CL on the expression, localization, membrane association, and complex assembly of Taz1p.…”

“…Newly synthesized CL undergoes a remodeling process, the end result of which is the incorporation of more unsaturated fatty acyl chains and the establishment of a high degree of acyl chain symmetry (Schlame et al, 2005). One pathway of CL remodeling is mediated by the CL transacylase, tafazzin (Taz1p; Xu et al, 2006b), the mutant gene product associated with the X-linked disease Barth syndrome (BTHS). BTHS is characterized by cardiac and skeletal myopathies and cyclic neutropenia (Barth et al, 1983(Barth et al, , 1999(Barth et al, , 2004; the disease presents in infants and if undiagnosed, is often fatal due to cardiac failure or sepsis.…”