Sharon Ackerman

---

Associate Professor Chaperone-mediated protein assembly Ph.D., New York University, NY, NY, 1987 e-mail: sackerm@med.wayne.edu Tel: 313-577-5016

The energy requirements of eukaryotic cells are met principally through the action of the ATP synthase, a large multimeric enzyme of the inner mitochondrial membrane. The ATP synthase is composed of an integral membrane proton pump (F₀) and a peripheral moiety (F₁) that catalyzes ATP synthesis coupled to proton translocation through F₀. Assembly of mitochondrial F₁ is dependent on the action of two nuclear gene products, Atp11p and Atp12p, which serve as molecular chaperones in this process. Under normal conditions, F₁ Assembly proceeds with the incorporation of five different types of subunits to form the oligomer (α 3β 3γ δ ε). The binding of Atp11p to unassembled β subunits and of Atp12p to unassembled α subunits is a key step in the assembly pathway, as it is through such actions that the chaperone proteins prevent the formation of non-productive (α)n and (β)n complexes and foster fruitful interactions between α and β subunits. One aspect of the work ongoing in the laboratory is to provide information about the molecular mechanism of Atp11p and Atp12p, and on structure/function relationships in the chaperone proteins. Following our identification of the human genes that encode orthologs of Atp11p and Atp12p, and the determination that they are widely expressed in all tissues, it has also become our interest to study the physiological effects in human cells that accompany the loss of these proteins.