Quality Control of Mis-localized
In addition to metabolic perturbations, a breakdown in organelle function also influences cellular health by altering protein homeostasis within cells. Cells must synthesize, fold, and deliver proteins to their proper intracellular destination—failure to do so results in severe cellular toxicity, and also functions as a driver of aging and age-related disorders. A prime example of this comes from mitochondria. Almost all mitochondrial resident proteins are synthesized on cytosolic ribosomes, and imported into mitochondria co- or post-translationally. Cytosolic precursor proteins cannot be imported into dysfunctional mitochondria—thus, a major consequence of mitochondrial impairment in cells is the toxic accumulation of non-imported mitochondrial precursor proteins. Current work in our lab is focused on elucidating mechanisms by which cells combat stress caused by non-imported mitochondrial proteins, and understanding whether these toxic precursors function as a driver of age-related disorders. Our recent results suggest that other organelles serve as triage centers for non-imported mitochondrial precursors, and may play a key role in protecting the cell during times of mitochondrial impairment.