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Mitophagy Research: The Ragusa Lab
An Introduction to Mitophagy
In order for a wide variety of cells to maintain homeostasis, their long-lived and toxic cellular components must be degraded. However, large protein aggregates and long-lived organelles can throw a wrench in things: due to their size, they are completely inaccessible to the proteasome, the major protein degradation machinery in the cell. To address this issue, cells degrade large cytosolic material through a process called autophagy, in which double membrane vesicles engulf cytoplasmic material and target it to the vacuole or lysosome for degradation. This process is conserved across eukaryotes [cite]. The sequestering of autophagic cargo can occur by either a non-selective (bulk) or a selective mechanism. Selective autophagy- our process of interest- can lead to the capture of mitochondria, peroxisomes, lipid droplets, large protein aggregates and intracellular pathogens. We are particularly interested in the initiation of mitophagy (mitochondria-selective autophagy), and study this process in yeast; using protein crystallography, NMR spectroscopy, small angle X-ray scattering, biochemistry, and cell biology to dissect the molecular mechanisms.
The malfunction of selective autophagy has been correlated with tumorigenesis, chronic infection and neurodegeneration. Gaining an understanding of the molecular mechanisms of selective autophagy will enable the development of novel therapeutics for related cancers, infectious disease, and neurodegenerative disease.