Does the beta subunit of mitochondrial trifunctional protein modulate monolysocardiolipin acylation to cardiolipin?

The alpha subunit of mitochondrial trifunctional protein (αTFP) catalyzes the acylation of monolysocardiolipin (MLCL) to cardiolipin (CL). We determined whether the beta subunit of mitochondrial trifunctional protein (βTFP) impacted the ability of αTFP to promote CL resynthesis from MLCL. Purified recombinant αTFP, but not βTFP, exhibited in vitro acylation of MLCL to CL with [1-14C]linoleoyl-Coenzyme A. Incubation of both αTFP and βTFP together did not alter the ability of αTFP to catalyze the in vitro acylation of MLCL to CL with [1-14C]linoleoyl-Coenzyme A. Hela cells were transfected with recombinant αTFP, βTFP or both then incubated with [1-14C]linoleate and radioactivity incorporated into CL determined. Expression of αTFP increased [1-14C]linoleate incorporation into CL 2-fold (p<0.05) whereas expression of βTFP did not affect [1-14C]linoleate incorporation into CL. Expression of both αTFP and βTFP together increased [1-14C]linoleate incorporation into CL to an identical level to that achieved with αTFP alone. Barth Syndrome (BTHS) patient lymphoblasts, which exhibit elevated MLCL and reduced CL, were incubated with βTFP inhibitory RNA and CL mass determined. Incubation of BTHS lymphoblasts with βTFP inhibitory RNA increased CL mass 1.5-2-fold (p<0.05). We hypothesize that the βTFP may regulate CL resynthesis in vivo in BTHS lymphoblasts.