title: Mitochondrial fission controls DNA fragmentation by regulating endonuclease G.
abstract: Mitochondria constantly undergo fusion and fission that are necessary for the maintenance of organelle fidelity. However, growing evidence has shown that abnormal mitochondrial fusion and fission participate in the regulation of apoptosis. Mitochondrial fusion is able to inhibit apoptosis, whereas mitochondrial fission is involved in the initiation of apoptosis. It remains elusive as to whether mitochondrial fission can regulate DNA fragmentation during apoptosis. Mitochondrial fission is triggered by dynamin-related protein-1 (Drp1), whereas mitofusin 1 (Mfn 1) is able to induce mitochondrial fusion. Here, we report that Drp1 is required for the release of endonuclease G from mitochondria. Knockdown of Drp1 can attenuate DNA fragmentation. Our data further show that Mfn 1 prevents endonuclease G release from mitochondria and the consequent DNA fragmentation. Intriguingly, Mfn 1 could inhibit the activation of caspase-3 and caspase-9, which are necessary for endonuclease G translocation to the nucleus. Our results provide novel evidence that DNA fragmentation is regulated by the mitochondrial fission machinery.
authors.affiliation: Department of Physiology, Shantou University School of Medicine, Shantou 515031, China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Li
authors.forename: Danian
authors.initials: D
authors.lastname: Qin
authors.forename: Peifeng
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D053938:DNA Fragmentation; D034281:Dynamins / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D061945:Caspase Inhibitors; D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D053148:Caspase 3; D053453:Caspase 9; C519851:Dnm1l protein, rat; D034281:Dynamins