| First Author | Zhuravleva E | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 14 | Pages | 2685-97 |
| PubMed ID | 22586271 | Mgi Jnum | J:186657 |
| Mgi Id | MGI:5432849 | Doi | 10.1128/MCB.00312-12 |
| Citation | Zhuravleva E, et al. (2012) Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin remodeling and fatty liver development. Mol Cell Biol 32(14):2685-97 |
| abstractText | Acyl coenzyme A (acyl-CoA) thioesterases hydrolyze thioester bonds in acyl-CoA metabolites. The majority of mammalian thioesterases are alpha/beta-hydrolases and have been studied extensively. A second class of Hotdog-fold enzymes has been less well described. Here, we present a structural and functional analysis of a new mammalian mitochondrial thioesterase, Them5. Them5 and its paralog, Them4, adopt the classical Hotdog-fold structure and form homodimers in crystals. In vitro, Them5 shows strong thioesterase activity with long-chain acyl-CoAs. Loss of Them5 specifically alters the remodeling process of the mitochondrial phospholipid cardiolipin. Them5(-/-) mice show deregulation of lipid metabolism and the development of fatty liver, exacerbated by a high-fat diet. Consequently, mitochondrial morphology is affected, and functions such as respiration and beta-oxidation are impaired. The novel mitochondrial acyl-CoA thioesterase Them5 has a critical and specific role in the cardiolipin remodeling process, connecting it to the development of fatty liver and related conditions. |
