Cardiolipin Affects the Supramolecular Organization of ATP Synthase in Mitochondria

Abstract

F(1)F(0) ATP synthase forms dimers that tend to assemble into large supramolecular structures. We show that the presence of cardiolipin is critical for the degree of oligomerization and the degree of order in these ATP synthase assemblies. This conclusion was drawn from the statistical analysis of cryoelectron tomograms of cristae vesicles isolated from Drosophila flight-muscle mitochondria, which are very rich in ATP synthase. Our study included a wild-type control, a cardiolipin synthase mutant with nearly complete loss of cardiolipin, and a tafazzin mutant with reduced cardiolipin levels. In the wild-type, the high-curvature edge of crista vesicles was densely populated with ATP synthase molecules that were typically organized in one or two rows of dimers. In both mutants, the density of ATP synthase was reduced at the high-curvature zone despite unchanged expression levels. Compared to the wild-type, dimer rows were less extended in the mutants and there was more scatter in the orientation of dimers. These data suggest that cardiolipin promotes the ribbonlike assembly of ATP synthase dimers and thus affects lateral organization and morphology of the crista membrane.

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

“…Indeed, these mitochondria exhibited increased electron density with less and disorganized cristae (Figure 2e), which is in agreement with previously published results. [33][34][35][36][37] In addition to reduction in cyt c, we also observed a decrease in the protein level of MTCO1 (Figure 2b). A reduction in the amount of this labile protein suggests a defect in respiratory chain complex IV assembly.…”

Structure of the yeast F 1 F o -ATP synthase dimer and its role in shaping the mitochondrial cristae

“…On the basis of our computer simulations we propose that the curvature induced by the ATP synthase dimer in a simple lipid membrane is sufficient to drive the formation of long dimer rows, which would then give rise to highly curved membrane ridges and lamellar cristae. Although the lipid composition of the membrane may also play a role (41), the fact that a tetramer of dimers can bend a lipid bilayer composed of only POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) into a ridge suggests that the dimer alone is perfectly adequate to drive its own self-association without the need for additional proteinprotein or protein-lipid interactions.…”

Unremodeled and Remodeled Cardiolipin Are Functionally Indistinguishable in Yeast

“…4 a mitochondrial phospholipid with two phosphate headgroups and four acyl chains, is required for the optimal function of numerous mitochondrial processes, including oxidative phosphorylation (OXPHOS) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13), protein import (14 -17), establishment of cristae morphology (18,19), fission and fusion (20 -22), and apoptosis (23,24). Despite limited acyl chain specificity of the CL biosynthetic enzymes (25,26), the acyl chain composition of CL within an organism or cell type displays a remarkable degree of homogeneity (27).…”