title: Cardiolipin and mitochondrial carriers.
abstract: Members of the mitochondrial carrier family interact with cardiolipin (CL) as evident from a variety of functional and structural effects. CL stabilises carrier proteins on isolation with detergents, with the P(i) carrier as the prime example. CL is required for transport in reconstituted vesicles, prime examples are the P(i)- and ADP/ATP carrier (AAC). CL binds to the AAC in a graded manner; 6 CL/AAC dimer bind tightly as measured on the (31)P NMR time scale. 2 additional CL/dimer bind reversibly and a fast exchanging envelope of phospholipids includes CL as measured on the ESR time scale. In the crystal structure of the CAT-AAC complex 3 CL bind to the periphery of the AAC in a three-fold pseudo-symmetry. The binding of CL is implicated to contribute lowering the high transition energy barriers in the AAC. Para-functions of the AAC, as in the mitochondrial pore transition (MPT) and in cell death are linked to the CL binding of the AAC. Ca(++) or oxidants can sequester or destroy AAC bound CL, rendering AAC labile, allowing pore formation and degradation. Thus AAC, by being vital for energy transfer, constitutes an Achilles heel in the eukaryotic cell. AAC together with CL is also engaged in respiratory supercomplexes. Different from AAC the similarly structured uncoupling protein (UCP1) has no tightly bound CL, but CL addition lowers affinity of the inhibitory nucleotide binding that may contribute to the physiological regulation of the uncoupling activity by ATP.
authors.affiliation: Institut für Physiologische Chemie der Universität München, Germany. Klingenberg@med.uni-muenchen.de
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenberg
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D024101:Mitochondrial Proteins; D000226:Mitochondrial ADP, ATP Translocases