Dear Editor,

Bid, a BH3-only proapoptotic member of the Bcl-2 family, and the carboxyl terminus of its cleavage product, tBid, are essential regulators of early mitochondrial apoptotic events and release of pro-apoptotic factors into the cytosol.1 Bid and tBid have a high-affinity binding domain for a mitochondria-specific phospholipid, cardiolipin (CL).2, 3, 4, 5 In normal cells, CL is predominantly localized in the inner membrane and contact sites. It plays a very important role in the assembly and maintenance of functionally active respiratory complexes (I, III and IV and F0/F1-ATPase) in the mitochondrial membrane and in normal operation of other mitochondrial multicomponent machines such as adenine nucleotide translocator, as well as tricarboxylate, pyruvate and phosphate carriers.6, 7, 8, 9 Decreased levels of CL caused by siRNA manipulations of CL synthase (CDP-diacylglycerol-phosphatidylglycerol phosphatidyltransferase) in cells were shown to result in disorganization of mitochondria and release of cytochrome c (cyt c) into the cytosol; these cells elicited enhanced sensitivity to proapoptotic stimuli.10 Recently, interactions of tBid with CL have been implicated as major players in orchestrating apoptotic changes in mitochondrial electron transport as well as activation of pro-apoptotic proteins Bak and Bax.5, 11 During apoptosis, however, CL undergoes significant hydrolysis whose products – mono-lysoCL (MCL) and di-lyso-CL (DCL) – accumulate.4, 12

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