Mitochondrial ATP synthase: architecture, function and pathology - PubMed (original) (raw)

Review

Mitochondrial ATP synthase: architecture, function and pathology

An I Jonckheere et al. J Inherit Metab Dis. 2012 Mar.

Abstract

Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F(1), situated in the mitochondrial matrix, and F(o), located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions.

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Figures

Fig. 1

Fig. 1

Human mitochondrial ATP synthase, or complex V, consists of two functional domains, F1 and Fo. F1 comprises 5 different subunits (three α, three β, and one γ, δ and ε) and is situated in the mitochondrial matrix. Fo contains subunits c, a, b, d, F6, OSCP and the accessory subunits e, f, g and A6L. F1 subunits γ, δ and ε constitute the central stalk of complex V. Subunits b, d, F6 and OSCP form the peripheral stalk. Protons pass from the intermembrane space to the matrix through Fo, which transfers the energy created by the proton electrochemical gradient to F1, where ADP is phosphorylated to ATP. One β subunit is taken out to visualize the central stalk

Fig. 2

Fig. 2

Complex V assembly and dimerization. The current working model is based on assembly of the c-ring followed by binding of F1, the stator arm, and finally of subunits a and A6L. Two ATP synthase monomers dimerize via the Fo sector, where subunits a, e, g, b and A6L stabilize the monomer-monomer interface

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