Iris Montes

Research/Areas of Interest

The ubiquitin proteasome system (UPS) is a system crucial for protein degradation and by extension protein homeostasis in eukaryotic cells. In the Raman lab we are interested in investigating how the evolutionarily conserved AAA-ATPase known as VCP (P97 in mammals) recognizes and degrades ubiquitin-modified substrates utilizing distinct adaptor proteins. These adaptors are essential for guiding VCP to ubiquitinated substrates. In particular to cellular sub-compartments such as the mitochondria. Mitochondria are profoundly integrated into essential functions of eukaryotic cells, including ATP production via oxidative phosphorylation, signaling pathways, biosynthesis of amino acids, lipids, and heme as well as programmed cell death. The vast majority of mitochondrial proteins (estimated to be ~ 1200) are encoded by nuclear genes, that are produced as precursors on cytosolic ribosomes. Their import into mitochondria is therefore vital for mitochondrial function and biogenesis. The translocase of the outer membrane (TOM) complex forms the entry gate for the import of the vast majority of nuclear encoded mitochondrial proteins making its surveillance for clogged precursors vital. For my project I will be investigating whether the VCP adaptor complexes monitor protein translocation on mitochondria by monitoring the TOM complex for stalled polypeptides in mammalian cells. This gate-keeper function would be a novel mechanism by which protein import into the mitochondria is monitored.