Atypical mitochondrial fission upon bacterial infection
ABSTRACT We recently showed that infection by Listeria monocytogenes causes mitochondrial network fragmentation through the secreted pore-forming toxin listeriolysin O (LLO). Here, we examine factors involved in canonical fusion and fission. Strikingly, LLO-induced mitochondrial fragmentation does not require the traditional fission machinery, as Drp1 oligomers are absent from fragmented mitochondria following Listeria infection or LLO treatment, as the dynamin-like protein 1 (Drp1) receptor Mff is rapidly degraded, and as fragmentation proceeds efficiently in cells with impaired Drp1 function. LLO does not cause processing of the fusion protein optic atrophy protein 1 (Opa1), despite inducing a decrease in the mitochondrial membrane potential, suggesting a unique Drp1- and Opa1-independent fission mechanism distinct from that triggered by uncouplers or the apoptosis inducer staurosporine. We show that the ER marks LLO-induced mitochondrial fragmentation sites even in the absence of functional Drp1, demonstrating that the ER activity in regulating mitochondrial fission can be induced by exogenous agents and that the ER appears to regulate fission by a mechanism independent of the canonical mitochondrial fission machinery.
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- "The LLO-induced mitochondrial fragmentation occurs at ER crossing sites. Furthermore, inhibition of actin polymerization during the LLO treatment decreases mitochondrial fragmentation, similar to INF2-mediated mitochondrial fission that requires actin assembly (Stavru et al., 2011; 2013). However, upon LLO treatment, DLP1 oligomers are lost from mitochondria and Mff is rapidly degraded, indicating that LLO-mediated mitochondrial fragmentation does not require conventional fission machinery. "
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