Differential stress responses of organelles to nutritional versus ER stress

About This Grant

Eukaryotic cells can rapidly adjust the abundance, size, and shape of their membrane-bound organelles in response to physiological needs. We recently found that fission yeast cells employ different mechanisms to counteract various types of stress: nutritional deprivation sequentially activates organelle degradation, while ER stress, caused by the accumulation of misfolded proteins, induces morphological changes in multiple organelles, such as the ER, Golgi, and mitochondria, without triggering their degradation. Our current research aims to understand the molecular framework underlying these differential adaptive responses in fission yeast and to investigate their conservation in mammalian systems. We propose that organelles communicate and coordinate sequential degradation through selective autophagy. To explore this, we will integrate structural prediction with genetic and cellular assays to systematically identify selective autophagy receptors and use multi-omics approaches to investigate potential crosstalk between organelles during starvation. Given that ER stress is increasingly recognized as a contributing factor in a number of human diseases including neurodegenerative disorders and cancer, we will also use fission yeast and human cell cultures to examine how these cells reorganize multiple organelles to mitigate ER stress. These insights could advance our understanding of disease pathology and suggest new diagnostic and therapeutic strategies.