Supercomplexes and subcomplexes of mitochondrial oxidative phosphorylation

Abstract

Dimerization or oligomerization of ATP synthase has been proposed to play an important role for mitochondrial cristae formation and to be involved in regulating ATP synthase activity. We found comparable oligomycin-sensitive ATPase activity for monomeric and oligomeric ATP synthase suggesting that oligomerization/monomerization dynamics are not directly involved in regulating ATP synthase activity. Binding of the natural IF1 inhibitor protein has been shown to induce dimerization of F1-subcomplexes. This suggested that binding of IF1 might also dimerize holo ATP synthase, and possibly link dimerization and inhibition. Analyzing mitochondria of human rho zero cells that contain mitochondria but lack mitochondrial DNA, we identified three subcomplexes of ATP synthase: (i) F1 catalytic domain, (ii) F1-domain with bound IF1, and (iii) F1-c subcomplex with bound IF1 and a ring of subunits c. Since both IF1 containing subcomplexes were present in monomeric state and exhibited considerably reduced ATPase activity as compared to the third subcomplex lacking IF1, we postulate that inhibition and induction of dimerization of F1-subcomplexes by IF1 are independent events. F1-subcomplexes were also found in mitochondria of patients with specific mitochondrial disorders, and turned out to be useful for the clinical differentiation between various types of mitochondrial biosynthesis disorders. Supramolecular associations of respiratory complexes, the "respirasomes", seem not to be the largest assemblies in the structural organization of the respiratory chain, as suggested by differential solubilization of mitochondria and electron microscopic analyses of whole mitochondria. We present a model for a higher supramolecular association of respirasomes into a "respiratory string".

Invertebrates Mitochondrial Function and Energetic Challenges

“…Recent findings have also confirmed the existence of dynamic mitochondrial supercomplexes -defined as the association of protein complexes distributed along the inner mitochondrial membrane -on mammals, plants, yeasts (Yarrowia lipolytica), and bacteria (Nübel et al, 2009;Dudkina et al, 2010). Complexes I, III and IV are able to associate in order to promote electron transport as single OXPHOS complexes or else as a supercomplex called respirasome (I + III 2 + IV 1-2 ) both of which can autonomously carry out respiration (Wittig et al, 2006). Furthermore, complex V -the mitochondrial F 1 F O ATP-synthase -is associated to form dimeric, trimeric and tetrameric organisations (Dudkina et al, 2008).…”

Restricted diffusion of OXPHOS complexes in dynamic mitochondria delays their exchange between cristae and engenders a transitory mosaic distribution

“…OXPHOS complexes I, III and IV assemble in supercomplexes of different stoichiometry (Schägger and Pfeiffer, 2000;Eubel et al, 2004;Dudkina et al, 2005;Schäfer et al, 2006;Wittig et al, 2006;Althoff et al, 2011), while dimers of F 1 F 0 ATP synthase often organize in row like structures in cristae membranes (Davies et al, 2011). According to the Saffman-Delbrück model, the translational mobility is independent of the amount by which the particle sticks out of the membrane sheet (Saffman and Delbrück, 1975) and diffusion coefficients of membrane domains are only logarithmically related to domain radii suggesting little influence (Petrov and Schwille, 2008).…”

ATP Synthase Complex of Plasmodium falciparum

“…(iii) ATP synthase complex may participate in mitochondrial morphogenesis. Studies in other systems (57,(62)(63)(64)(65) have shown that formation of respiratory supercomplexes is required for functional morphogenesis of mitochondria. Dimerization of the ATP synthase complex has been shown to be critical for the curvature of mitochondrial cristae (17,19,66).…”