Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Tuesday Speaker Abstracts

MECHANISMS AND SIGNIFICANCE OF TISSUE-SPECIFIC MITOCHONDRIAL CALCIUM UPTAKE Ming-Feng Tsai 1 ; Chen-Wei Tsai 1 ; Madison Rodriguez 1 ; 1 University of Colorado Anschutz Medical Campus, Physiology and Biophysics, Aurora, CO, USA Mitochondrial calcium uptake, mediated by the mitochondrial Ca 2+ uniporter, regulates oxidative phosphorylation, apoptosis, and intracellular Ca 2+ signaling. It is believed that cells exclusively use a MICU1-MICU2 heterodimer to complex with the uniporter to define mitochondrial Ca 2+ uptake properties. This picture, however, is oversimplified. Here, we demonstrate that skeletal muscle and kidneys equip uniporters with a MICU1 homodimer, and that human/rodent cardiac uniporters are devoid of MICUs. Cells control the population of uniporters with MICU1 homo- and heterodimers by manipulating MICU1/MICU2 importation into mitochondria, and protect correctly-assembled MICU1 dimers by catalyzing an intersubunit disulfide to block proteolysis. For cells, the choice of MICUs presents a trade-off. Using MICU1 homodimer or eliminating MICUs allows mitochondria to more readily import Ca 2+ to enhance ATP production, but these cells have elevated ROS, impaired basal metabolism, and higher susceptibility to death.

UNCOVERING AND REPROGRAMMING ALLOSTERIC SIGNAL TRANSDUCTIONS IN GPCRS Patrick Barth EPFL, Switzerland No Abstract

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