Seminar Title: “From Extracellular Matrix to High-Capacity Mitochondria”

Dr. David R. Sherwood, Ph.D.

Jerry G. and Patricia Crawford Hubbard Professor and Associate Chair of Biology, Duke University

Abstract: My lab studies how cells interact with basement membrane, a conserved extracellular matrix scaffolding that enwraps and supports tissues. We use C. elegans simplicity, transparency, and genetic manipulation to examine how basement membranes form, stretch, attach tissues, and age. Our group also investigates how cells invade through basement membrane. Cell invasion is a normal developmental and physiological process that is hijacked by tumor cells to initiate metastasis. Anchor Cell (AC) invasion in C. elegans is a simple in vivo model to dissect the mechanisms underlying invasion in real-time. The genetic pathways and cellular mechanisms driving AC invasion are shared with cancer cells, including expression of matrix-metalloproteinases that break down basement membrane and F-actin rich invadopodial membrane protrusions that breach basement membrane barriers. We recently discovered that mitochondria are enriched at the invasive cell membrane of the AC and produce a burst of ATP to fuel polymerization of branched F-actin networks required for invadopodial-membrane protrusions. To further understand how cell metabolism powers invasion, we are investigating mechanisms of nutrient acquisition, mitochondria regulation, and ATP dynamics. I will present recent work showing how energy acquisition and use are integrated into the cell invasion program. Strikingly, by generating a mitochondrial toolkit of over 20 mitochondrial proteins tagged with mNeonGreen, we discovered that the AC harbors specialized mitochondria that deliver high levels of ATP to fuel the invasive machinery.  This mitochondrial toolkit is now also providing insight into the remarkable regulation and diversity of mitochondria in other cellular processes.

This event is part of the Morgridge Metabolism Colloquium.