Autophagy

Autophagy

p62/SQSTM1 can be considered one of the archetypical autophagy receptors that are centrally involved in the recognition and subsequent disposal of ubiquitinated cargo through autophagy. Moreover, p62 is also known to act in a wide range of signaling activities affecting nutrient sensing, oxidative stress, infection, immunity and inflammation. Over the last decade, we have shown that p62 forms double-helical filamentous structures by an N-terminal PB1 domain-scaffold that hosts a C-terminal binding platform with critical interaction motifs (Ciuffa et al. 2015, Jakobi et al., 2020, Berkamp et al. 2025). In the cellular environment, p62 has been localized in so-called p62 bodies that were shown to display properties of liquid-liquid phase separation (reviewed in Berkamp, Mostafavi et al. 2020). Recently, we visualized enriched p62 bodies together with a Ca-rich layer encapsulating lipid droplet cargo in the native environment of the cell (Berkamp et al., 2025). We study the structural biology of p62 and will further shed light on their structural and functional involvement in the early stages of autophagy.

  • Berkamp, S., Jungbluth, L., Katranidis, A., Mostafavi, S., Korculanin, O., Lu, P.-H., Ickert, L., Dierig, M.M., Sharma, L., Thukral, L., Huesgen, P.F., Kononenko, N.L., Fitter, J., Dunin-Borkowski, R.E., Sachse, C., 2025. Structural organization of p62 filaments and the cellular ultrastructure of calcium-rich p62-enwrapped lipid droplet cargo. Nat Commun 16, 10810.
  • Berkamp S., Mostafavi S., and Sachse C. (2020) Structure and Function of p62/SQSTM1 in the emerging framework of phase separation. FEBS Letters doi: 10.1111/febs.15672.
  • Jakobi A.J., Huber S.T., Mortensen S.A., Schultz S.W., Palara A., Kuhm T., Shrestha B.K., Lamark T., Hagen W.J.H., Wilmanns M., Johansen T., Brech A., and Sachse C. (2020) Structural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake. Nat Commun 11(1):440.
  • Ciuffa, R., Lamark, T., Tarafder, A.K., Guesdon, A., Rybina, S., Hagen, W.J.H., Johansen, T., and Sachse, C. The Selective Autophagy Receptor p62 Forms a Flexible Filamentous Helical Scaffold. (2015) Cell Rep 11, 748–758.

Last Modified: 26.12.2025