Modulation of the host cell mitochondrial proteome by PemKSa toxin protein exposure

Abstract

Mitochondria are essential organelles involved in abundant cellular functions ranging from energy metabolism to cell survival. The inhibition of these mitochondrial functions by bacterial toxin proteins promotes disease and inhibits cell growth. Prominent evidence proposes that mitochondria provide a platform for innate immune response signalling pathways. To investigate how a bacterial toxin manipulates the mitochondrial environment of the host Caenorhabditis elegans at the molecular level, a quantitative proteomic study of mitochondria following exposure to the PemKSa toxin was performed. In this study, we purified C. elegans mitochondria and performed a comprehensive proteomic analysis using a shotgun proteomic approach (LC-MS/MS). LC-MS/MS data were analysed using various bioinformatics tools, which revealed the role and involvement of several regulatory proteins and pathways associated with mitochondrial functions. We detected variation in protein expression in key metabolic pathways, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, carbon metabolism, glycolysis and apoptosis, which suggests global reprogramming of host mitochondria metabolism by the toxin. Our results provide new horizons for mitochondria-associated protein functions and the classification of mitochondrial diseases during host-toxin interactions.