title: 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.
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, 75015 Paris, France.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Stavru
authors.forename: Amy E
authors.initials: AE
authors.lastname: Palmer
authors.forename: Chunxin
authors.initials: C
authors.lastname: Wang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Youle
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D001427:Bacterial Toxins / Q000032:analysis / Q000633:toxicity*; D015153:Blotting, Western; D034281:Dynamins; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000032:analysis / Q000633:toxicity*; D006460:Hemolysin Proteins / Q000032:analysis / Q000633:toxicity*; D006801:Humans; D008089:Listeria monocytogenes / Q000737:chemistry*; D008088:Listeriosis / Q000503:physiopathology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; C110768:DNM1L protein, human; D034281:Dynamins; C038705:hlyA protein, Listeria monocytogenes
keywords: actin; live cell imaging; mitochondrial dynamics
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