Parkin_mediated_mitophagy_is_induced_by_the_probiotics_Saccharomyces_boulardii_and_Lactococcus_lactis
Description
Dysfunctional mitochondria are a hallmark feature of neurodegenerative disorders, such as Parkinson’s disease, and upregulation of Parkin-mediated mitophagy pathways serve to remove unhealthy mitochondria from cells. Probiotics have been used to alleviate symptoms of Parkinson’s disease and there is evidence to suggest that they modulate mitochondrial pathways. In this study, we conducted a screen of 49 probiotics and tested various stages of mitophagy to determine whether any of the probiotics can upregulate mitophagy in cells sustaining mitochondrial damage. We found that two probiotics, Saccharomyces boulardii and Lactococcus lactis upregulate mitochondrial Parkin recruitment, phospho-ubiquitination, and mitofusin degradation. Further, these strains increase lysosomal degradation of dysfunctional mitochondria in the brain of Drosophila that were subjected to the mitochondrial toxin paraquat, and also improve longevity and motor function in this Drosophila model of Parkinson’s disease. These effects occur due to exogenous soluble factors that are released by probiotics under laboratory conditions. We identified methyl-isoquinoline-6-carboxylate as one such molecule, which upregulates mitochondrial parkin recruitment, phospho-ubiquitination, mitofusin degradation, and lysosomal degradation, while restoring motor function in paraquat-treated flies. These data suggest a novel mechanism that probiotics use to stimulate mitophagy through a Parkin-dependent pathway that could potentially be utilized to treat neurological diseases at an early stage.