title: Differential reduction in cardiac and liver monolysocardiolipin acyltransferase-1 and reduction in cardiac and liver tetralinoleoyl-cardiolipin in the α-subunit of trifunctional protein heterozygous knockout mice.
abstract: The contribution of α-subunit of trifunctional protein (αTFP) to cardiolipin (CL) (diphosphatidylglycerol) remodelling and mitochondrial supercomplex formation was examined in heart and liver mitochondria from wild-type (WT) and αTFP heterozygous knockout [Mtpa(+/-)] mice. Mtpa(+/-) mouse heart and liver exhibited an approximate 55% and 50% reduction in αTFP protein expression compared with WT respectively. Monolysocardiolipin (MLCL) acyltransferase (MLCL AT)-1 protein derived from αTFP was reduced by 30% in Mtpa(+/-) mouse heart but not in liver compared with WT. In vitro acylation of MLCL was significantly reduced in heart but not in liver mitochondria of Mtpa(+/-) mice compared with WT. CL mass was reduced and significant reductions in linoleate-containing CL species, in particular tetralinoleoyl-CL (L4-CL) and trilinoleoyl-CL (L3-MLCL) species, were observed in heart and liver mitochondria of Mtpa(+/-) mice compared with WT. Cardiac and liver mitochondrial supercomplex assembly and NADH dehydrogenase (complex I) activity within these supercomplexes were unaltered in both Mtpa(+/-) mouse heart and Mtpa(+/-) mouse liver compared with WT. The results indicate that αTFP may modulate CL molecular species composition in murine heart and liver. In addition, L4-CL might not be an essential requirement for mitochondrial supercomplex assembly.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T6.
authors.forename: Edgard M
authors.initials: EM
authors.lastname: Mejia
authors.affiliation: Department of Medicine, University of Missouri, Columbia, MO 65211, U.S.A.
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
authors.affiliation: Department of Medicine, Division of Cardiology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, CO 80045, U.S.A.
authors.forename: Genevieve C
authors.initials: GC
authors.lastname: Sparagna
authors.affiliation: Department of Biochemistry, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T6 DREAM, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, Manitoba, Canada, R3E 3P4 ghatch@chrim.ca.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Hatch
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D063992:Mitochondrial Trifunctional Protein, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; C523441:tetralinoleoylcardiolipin; D063992:Mitochondrial Trifunctional Protein, alpha Subunit; D000217:Acyltransferases; C401969:monolysocardiolipin acyltransferase; D042967:Electron Transport Complex I
keywords: acyltransferase; alpha subunit; cardiolipin; heart; liver; lysocardiolipin; monolysocardiolipin; trifunctional protein