Listeria monocytogenes exploits the MICOS complex subunit Mic10 to promote mitochondrial fragmentation and cellular infection

Abstract : Mitochondrial function adapts to cellular demands and is affected by the ability of the organelle to undergo fusion and fission in response to physiological and non-physiological cues. We previously showed that infection with the human bacterial pathogen Listeria monocytogenes elicits dramatic mitochondrial fission and causes a decrease in the mitochondrial membrane potential. Using quantitative proteomics of purified mitochondria, we searched for host factors involved in L. monocytogenes-induced mitochondrial fission. We found that Mic10, a critical component of the mitochondrial contact site and cristae organizing system (MICOS) complex is significantly enriched in mitochondria isolated from cells infected with wild-type L. monocytogenes, but not with mutant bacteria not expressing the pore-forming toxin listeriolysin O. Increased mitochondrial Mic10 levels did not correlate with upregulated gene transcription, suggesting a post-transcriptional regulatory mechanism. We show that Mic10 is necessary for L. monocytogenes-induced mitochondrial network fragmentation, and that it contributes to L. monocytogenes cellular infection independently of MICOS proteins Mic13, Mic26 and Mic27. Together, L. monocytogenes infection allowed us to uncover a role for Mic10 in mitochondrial fission.