Correlation between losses of mitochondrial ATPase activity and cardiolipin degradation

Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome

“…Alterations in cardiolipin have previously been associated with the regulation of electron transport chain complex components as well as several other pivotal metabolic enzymes in the mitochondrial membrane (71)(72)(73)(74)(75)(76)(77). Previously, a decrease in Complex III activity in Barth syndrome fibroblasts from two patients was reported in addition to several other minor metabolic deficiencies ( 78 ).…”

Cardiolipin binds selectively but transiently to conserved lysine residues in the rotor of metazoan ATP synthases

“…However, the residence times of cardiolipin molecules with the ring were brief and sufficient for the rotor to turn only a fraction of a degree in the active enzyme. With the demethylated c 8 -ring and with c 10 -and c 11 -rings, the density of bound cardiolipin molecules at this site increased, but residence times were not changed greatly. These highly specific but brief interactions with the rotating c-ring are consistent with functional roles for cardiolipin in stabilizing and lubricating the rotor, and, by interacting with the enzyme at the inlet and exit of the transmembrane proton channel, in participation in proton translocation through the membrane domain of the enzyme.…”

“…Larger rings of known structure, from c 9 -c 15 in eubacteria and chloroplasts, conserve either a lysine or an arginine residue in the equivalent position. In computer simulations of hydrated membranes containing trimethylated or unmethylated bovine c 8 -rings and bacterial c 10 -or c 11 -rings, the head-groups of cardiolipin molecules became associated selectively with these modified and unmodified lysine residues and with adjacent polar amino acids and with a second conserved lysine on the opposite side of the membrane, whereas phosphatidyl lipids were attracted little to these sites. However, the residence times of cardiolipin molecules with the ring were brief and sufficient for the rotor to turn only a fraction of a degree in the active enzyme.…”

Cardiolipin puts the seal on ATP synthase

“…Already in 1973, Santiago et al (12) established a correlation between the presence of CL and the level of ATP synthase activity in mitochondria. Two decades later, solid-state NMR (ssNMR) suggested a high affinity interaction between F o F 1 -ATPase and CL (13).…”