Role of cardiolipin in mitochondrial carriers

All mitochondrial carriers are likely to have three tightly bound cardiolipin molecules, which are important for their structure and mechanism.

Figure Three cardiolipin molecules, shown in sphere representation, are tightly bound to the mitochondrial ADP/ATP carrier.

The cardiolipins are positioned with their phosphate groups at the N-terminal ends of the even-numbered and matrix α-helices [1][2]. The phosphate moieities of cardiolipin provide hydrogen-bonding partners to the amide groups at the N-terminal ends of the helices, which are formed by glycine residues of the [YWF][KR]G and [YF]xG motifs [2]. Leaving unsatisfied hydrogen bond donors in a hydrophobic environment would be energetically unfavourable, and thus the cardiolipins act as a cap. The position of the cardiolipin phosphate groups also allows a favourable interaction with the positively charged side of the helix dipoles, stabilizing binding of cardiolipin, which is likely to carry two negative charges at physiological pH [2]. Recently we have shown that uncoupling proteins, which are of the same protein family, also have tightly bound cardiolipins [3].

We are interested in understanding the role of cardiolipin in the transport mechanism of mitochondrial carriers.

 
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Movie The two phosphate moieties of cardiolipin are bound to the mitochondrial ADP/ATP carrier via hydrogen bonds (cyan) and the positive dipoles (dark blue) at the N-termini of the even-numbered and matrix α-helices.  The glycine residues of the [YWF][KR]G (purple) and [YF]xG motifs (green) are helix breakers [2].


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