Biophysical Society Conference | Tahoe 2023

Proton Reactions: From Basic Science to Biomedical Applications

Wednesday Speaker Abstracts

MITOCHONDRIAL ATP/ADP CARRIER – PROTON OR FATTY ACID ANION TRANSPORTER? Elena E. Pohl Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria The mitochondrial ATP/ADP carrier (ANT) belongs to the family of SLC25 solute carriers. It transports not only purine nucleotides but also protons across the inner mitochondrial membrane. The exact mechanism of this transport is not known. I will discuss two groups of putative mechanisms that describe ANT as either (i) a proton carrier that functions in the presence of long chain fatty acids (FA) or other uncouplers or (ii) a FA anion transporter. In the former case, the FA acid is bound to the protein, and its carboxyl group fills a gap in the wire of proton relay moieties. In the latter case, the proton is translocated by the neutral form of FA, which carries it from the matrix to the intermembrane space (fatty acid cycling hypothesis). Our recent results support this hypothesis [1]. We propose a four-step mechanism for the “sliding” of the FA anion from the matrix to the mitochondrial intermembrane space [2]. The research was supported by Austrian Science Fund (P31559-B20). 1. Kreiter, J., et al., Int J Mol Sci, 2021. 22 (5). 2. Kreiter, J., et al., bioRxiv, 2022: p. 2022.06.27.497434. PROTON GATING OF GPCR SIGNALING Daniel G. Isom 1,2,3 ; 1 University of Miami Miller School of Medicine, Molecular and Cellular Pharmacology, Miami, FL, USA 2 University of Miami, Sylvester Comprehensive Cancer Center, Tumor Biology Program, Miami, FL, USA 3 University of Miami, Institute for Data Science and Computing, Coral Gables, FL, USA In all domains of life, proton signals are essential, yet poorly understood regulators of cell biology and macromolecular function. Prominent examples include coincident acid signals that regulate protein activity in endosomes, inflammatory zones, and tumor microenvironments. In my seminar, I will show that these coincident signals regulate many G protein-coupled receptors (GPCRs), the largest and most therapeutically targeted family of transmembrane receptors in humans. Additionally, I will present the molecular basis of GPCR proton sensing and showcase the data science, synthetic biology, and biophysical insight that drive our interdisciplinary research program.

39