Compositions and methods for determining interactions of mitochondrial components, and for identifying agents that alter such interactions
AssigneeMitoKor
InventorsAnne N. Murphy, William Clevenger, Sandra Eileen Wiley, Alexander Y. Andreyev, Luciano G. Frigeri, Gonul Velicelebi, Robert E. Davis
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Abstract
Compositions and methods are provided for identifying agents that alter mitochondrial membrane permeability transition. The screening methods generally detect agents that alter the interaction between the mitochondrial adenine nucleotide translocator and cyclophilin D. Such agents may be used, for example, in the treatment of a variety of conditions associated with altered mitochondrial function.
Claims17
A method of identifying an agent that alters binding of an adenine nucleotide translocator polypeptide to a cyclophilin polypeptide, comprising:
- (a) contacting, in the absence and presence of a candidate agent, (i) a first isolated recombinant polypeptide comprising a cyclphilin polypeptide or variant thereof with (ii) a sample comprising a second isolated recombinant polypeptide that comprises a recombinant human adenine nucleotide translocator polypeptide or variant thereof, under conditions and for a time sufficient to permit the cyclophilin polypeptide, the adenine nucleotide translocator polypeptide and the candidate agent to interact;
- and
- (b) comparing a level of binding of the first isolated recombinant polypeptide to the second isolated recombinant polypeptide in the absence of the candidate agent to the level of binding of the first isolated recombinant polypeptide to the second isolated recombinant polypeptide in the presence of the candidate agent, wherein a decreased level of binding in the presence of the agent indicates an agent that inhibits binding of an adenine nucleotide translocator polypeptide to a cyclophilin polypeptide and wherein an increased level of binding in the presence of the agent indicates an agent that enhances binding of an adenine nucleotide translocator polypeptide to a cyclophilin polypeptide, and therefrom identifying an agent that alters binding of an adenine nucleotide translocator polypeptide to a cyclophilin polypeptide.
Dependencies are inferred from the claim text.