Endosomal Microautophagy, a novel catabolic process
Proper turnover of proteins and organelles is essential for normal cell function. Global decline in the efficiency of cellular quality control systems leads to liver and neurodegenerative diseases e.g. due to protein aggregation, in particular at old age. Damaged or altered cytosolic proteins are cleared by the proteasome and autophagy. Importantly, autophagy also provides nutrients including amino acids and lipids to cells under stress conditions such as starvation, and is thus essential for energy balance.
There is a strong correlation between lifespan extension, age related diseases and levels of autophagy. Not surprisingly, autophagy declines with age and is associated with the accumulation of altered, defective components in all model organisms examined, including mice and Drosophila, and experimental reduction of autophagy in animal models leads to reduced organ function and a shortened life span.
Although Macroautophagy (MA) can selectively degrade organelles or aggregated proteins, selective degradation of single proteins has only been described for Chaperone Mediated Autophagy (CMA) and endosomal Microautophagy (eMI). CMA, presumed to exist only in mammals and birds, is specific for proteins containing a KFERQ-related targeting motif. eMI, the uptake of proteins into multivesicular bodies via the ESCRT machinery can occur in bulk and in a KFERQ dependent manner. In collaboration with the Cuervo lab in our department, we have identified an eMI-like pathway in Drosophila melanogaster. We are currently using the power of genetics to identify eMI regulators and to define its physiological role.
Because altered autophagy contributes to liver, kidney, and neurodegenerative diseases, our research will significantly advance our understanding of how dysfunction of eMI may cause disease, ultimately leading to the development of novel strategies for treatments.
