Origin of mitochondrial proton leak: comparative investigation of Adenine Nucleotide, Translocase, Phosphate and Aspartat/Glutamate Carriers

• Applicant: Professorin Dr. Elena E. Pohl
• Subject Area: Anatomy and Physiology
• Term: from 2007 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40116377

During oxidative phosphorylation protons are driven back into the matrix through the F1/F0-ATP synthase or return through alternative pathways (leak), lowering the efficiency of ATP synthesis. Origin and significance of the proton leak is not well understood. If catalyzed by members of uncoupling protein subfamily it results in nonshivering thermogenesis in brown adipose tissue (UCP1) or it may participate in the regulation of reactive oxygene species in other tissues (UCP2-UCP5). Experiments on isolated mitochondria indicate that also other mitochondrial carriers may significantly contribute to H+ leak. The latter will be investigated in the present project using model membranes reconstituted with highly purified proteins: adenine nucleotide translocase (ANT), phosphate (PIC) or (iii) aspartate/glutamate carriers (AGC). The modulating role of membrane lipid composition, transmembrane and dipole potentials will be studied. The necessity of the fatty acid binding to proteins will be proved by site-directed mutagenesis. Comparing the single molecule proton conductances of ANT, PIC, AGC and uncoupling proteins, their relative contributions to basal and inhibitor-sensitive membrane proton leaks will be evaluated.

• DFG Programme: Research Grants
• International Connection: Austria