José Luis Zúñiga Elizari / Ignacio Azcue
Salónn de Actos de Biogipuzkoa
25/10/24
13:30
GRN emerges as a pivotal regulator in response to metabolic stress. Current research indicates that GRN plays a crucial role in lysosomal biogenesis and function, which are essential for the cellular degradation pathways that manage waste. Our observations demonstrate that GRN is upregulated and localized to stress granules following metabolic stress, suggesting a protective mechanism activated in response to such challenges.
The significance of GRN becomes particularly evident when examining ribophagy, the selective autophagic degradation of ribosomes. Ribosomes serve as the cellular machinery for protein synthesis and must be tightly regulated to ensure that only functional and necessary proteins are produced, especially during periods of energy stress. In this context, small ribosomal subunits transport mRNA to stress granules, effectively stalling their translation.
We present compelling evidence that GRN facilitates the recruitment of autophagic machinery to ribosomes, thereby linking lysosomal function with the clearance of non-functional ribosomes. As stress granules form, they act as a double-edged sword: while they initially safeguard mRNAs and promote cellular survival, their accumulation can become toxic if unresolved. GRN plays a critical role in orchestrating the transition from survival to degradation by promoting the fusion of lysosomes with stress granules. This fusion process enables the degradation of both the stress granules and the associated ribosomes, effectively managing the cellular response to stress.
The intricate interplay among GRN, lysosomes, and autophagic pathways underscores a sophisticated regulatory mechanism. By facilitating the clearance of both ribosomes and stress granules, GRN ensures that cells can adapt and thrive even in the face of metabolic adversity.