CSB Faculty Candidate Seminar: Keunwoo Ryu, Ph.D., Wednesday, Feb 5, 2025, Munzer!
The Department of Chemical and Systems Biology Presents
Faculty Candidate Seminar
Keunwoo Ryu, Ph.D.
Memorial Sloan Kettering Cancer Center
Wednesday, February 5, 2025
10:00 AM – 11:00 AM (Pacific Time)
Munzer Auditorium
Talk Title: “Compartmentalization as a Regulator of Cellular Metabolism”
Talk Abstract: Metabolic pathways consist of numerous competing reactions and branch points, yet how cells efficiently coordinate these processes remains incompletely understood. Mitochondria play a vital role in cell growth and proliferation by supporting both ATP production through oxidative phosphorylation (OXPHOS) and the synthesis of macromolecular precursors. While OXPHOS primarily relies on the oxidation of tricarboxylic acid (TCA) cycle intermediates, the mitochondrial production of proline and ornithine depends on reductive synthesis. How cells simultaneously engage in these competing pathways within the same organelle is unclear. Using high-resolution imaging, metabolomics, and isotope tracing, we found that increased cellular dependence on OXPHOS triggers the sequestration of pyrroline-5-carboxylate synthase (P5CS), the rate-limiting enzyme in proline and ornithine synthesis, into a subset of mitochondria lacking ATP synthase. This sequestration is driven by both the intrinsic filament-forming properties of P5CS and the mitochondrial fusion and fission cycle. Failure to segregate these metabolic pathways through mitochondrial fusion and fission results in cells either sacrificing the capacity for OXPHOS while sustaining the reductive synthesis of proline, or foregoing proline synthesis while preserving adaptive OXPHOS. These findings reveal that compartmentalization within mitochondria enables cells to sustain competing metabolic reactions and highlights how mitochondrial dynamics adapt to fluctuating nutrient availability and bioenergetic demands to maintain cellular metabolism