Friday, April 26, 2024
4/26/2024
Mitochondria provide energy, execute key steps of metabolism, control calcium, and modulate cellular decisions for life/death. In light of these critical functions in cell, tissue, and organism health, it is not surprising that mitochondrial functionality plays an essential role in neuronal maintenance in everyday biology, aging, and late-onset neurodegenerative disease. Mitochondrial quality control is thought to be primarily executed through cell-internal elimination via mitophagy and lysosome degradation. However, the Driscoll lab has discovered, and recently published, that mitochondria can be thrown out of neurons in large membrane bound vesicles we call mito-exophers. Damaged mitochondria have been observed in exophers budding from C. elegans touch neurons; mitochondria can be observed in exophers extruded from C. elegans dopaminergic neurons as well. Genetic and pharmacological treatments that compromise mitochondria can increase numbers of exophers produced by touch neurons, suggesting that throwing away defective mitochondria may be a mechanism for neuronal quality control. Indeed, some mammalian neurons can throw out their mitochondria for degradation by neighboring astrocytes (Davis, PNAS 11:9633), suggesting relevance across phyla. My project will: 1) investigate the basic biology of mito-exopher production by defining when they are produced and quantitating features of retained vs. extruded mitochondria over lifetime; 2) test the roles of stress and Parkinson's disease homolog genes on mitochondrial quality and mito-exopher production; and 3) begin to address whether neurons that produce mito-exophers maintain better functionality and mitochondrial populations as compared to those that do not produce mito-exophers. My work will contribute to defining the foundation of a newly identified mechanism in mitochondrial quality control. I anticipate relevance to understanding neuronal maintenance and neuronal degeneration, especially as associated with perturbed mito- chondrial quality as may occur in Parkinson's disease and many other human disorders.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
