Atypical mitochondrial fission upon bacterial infection

Unité des Interactions Bactéries-Cellules, Institut Pasteur, 75015 Paris, France.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2013; 110(40). DOI: 10.1073/pnas.1315784110
Source: PubMed


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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    • "Second, as several proteins are known to tether ER-mitochondrial membranes (Rowland and Voeltz, 2012), the role of these proteins in promoting or disrupting Spire1C's interaction with INF2 also needs to be studied. Such interactions may underlie differences in the mode of mitochondrial division seen in cells undergoing apoptosis, mitophagy, mitosis, or in response to toxins such as LLO from Listeria (Chan, 2012; Hoppins and Nunnari, 2012; Youle and van der Bliek, 2012; Stavru et al., 2013). Finally, the precise organization of the actin meshwork responsible for constricting mitochondria needs to be characterized at higher resolution. "
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