On April 2, researchers led by Prof. ZHANG Hong from the Institute of Biophysics of the Chinese Academy of Sciences, published a new study in Autophagy, uncovering a novel mechanism by which autophagy activity is regulated in Caenorhabditis elegans. They identified IMPORTIN-13 (IPO-13) as a crucial factor that controls autophagy and lysosomal function by mediating the nuclear transport of the transcription factor LIN-15B.

The key steps of the autophagy process include autophagosome formation, fusion of the autophagosome with the lysosome, and lysosomal degradation. While transcriptional regulation of autophagy-related genes is known to play a central role in modulating this process, it has remained unclear whether additional transcriptional regulators are systematically involved during C. elegans development.

LIN-15B contains a THAP domain and plays roles in chromosome segregation, chromatin modification, and transcriptional regulation. The researchers found that IPO-13 acts as the nuclear import receptor for LIN-15B, transporting LIN-15B from the cytoplasm into the nucleus.

Under physiological conditions, LIN-15B is predominantly localized in the nucleus, where it suppresses the expression of genes related to the autophagy-lysosome pathway, maintaining low transcriptional levels of autophagy genes to ensure basal autophagy activity.

In ipo-13 mutants or starved worms, LIN-15B fails to efficiently enter the nucleus, leading to reduced nuclear levels of LIN-15B and consequently upregulated expression of autophagy genes, resulting in increased autophagic flux.

The study identified LIN-15B as a critical transcription factor regulating autophagy activity during C. elegans development, with its regulatory function depending on the nuclear transport protein IPO-13 to shuttle it from the cytoplasm into the nucleus-a process that is modulated by the organism's nutritional status.

This research uncovers a novel mechanism by which cells sense nutritional cues to regulate autophagy activity.

Model showing that IPO-13-mediated cytoplasm-to-nucleus transport of LIN-15B controls autophagy activity. (Image by ZHANG Hong's group)