The article “Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response” by Yasuhiro Fujioka, Yuko Noda, Atsushi Noda, Yukari Yamasaki, Rika Hayakawa, Kazuaki Okada, Takeshi Iwatsubo, Yoshinori Watanabe, and Nobuo N. Noda is a landmark contribution to molecular biology. Their work uncovers a novel redox-independent mechanism for NRF2 activation through ULK1-mediated phosphorylation of p62 at Ser349—a discovery that reshapes our understanding of cellular stress responses.
What sets this study apart is its exquisite use of high-speed atomic force microscopy (HS-AFM), where the NanoWorld USC‑F1.2‑k0.15 ultra-short cantilever was instrumental (https://www.nanoworld.com/Ultra-Short-Cantilevers-USC-F1.2-k0.15) . With its ultra-fast response and high-resolution capability, this probe enabled real-time visualization of dynamic molecular interactions at the nanoscale. The combination of biochemical rigor and nanotechnological precision allowed the team to capture critical conformational shifts in p62 and ULK1, validating their proposed mechanism with striking clarity.
The authors’ multidisciplinary approach, combining structural biology, live-cell imaging, and biophysics, is a masterclass in scientific innovation. This study not only deepens our knowledge of autophagy and stress signaling but also showcases how the right tools—like the USC‑F1.2‑k0.15—can push the boundaries of discovery.
EMBO J(2023)42: e113349 https://doi.org/10.15252/embj.2022113349
