title: Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy.
abstract: Mitophagy is thought to play an important role in mitochondrial quality control. Mitochondrial division is believed to occur first, and autophagosome formation subsequently occurs to enwrap mitochondria as a process of mitophagy. However, there has not been any temporal analysis of mitochondrial division and autophagosome formation in mitophagy. Therefore, the relationships among these processes remain unclear. We show that the mitochondrial division factor Dnm1 in yeast or Drp1 in mammalian cells is dispensable for mitophagy. Autophagosome formation factors, such as FIP200, ATG14, and WIPIs, were essential for the mitochondrial division for mitophagy. Live-cell imaging showed that isolation membranes formed on the mitochondria. A small portion of the mitochondria then divided from parental mitochondria simultaneously with the extension of isolation membranes and autophagosome formation. These findings suggest the presence of a mitophagy process in which mitochondrial division for mitophagy is accomplished together with autophagosome formation.
authors.affiliation: Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Shun-Ichi
authors.initials: SI
authors.lastname: Yamashita
authors.affiliation: Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Xiulian
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Hamasaki
authors.affiliation: Department of Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Akiko
authors.identifier: http://orcid.org/0000-0002-6902-6749
authors.initials: A
authors.lastname: Nezu
authors.affiliation: Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Otera
authors.affiliation: Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Saigusa
authors.affiliation: Department of Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tamotsu
authors.identifier: http://orcid.org/0000-0001-9787-3788
authors.initials: T
authors.lastname: Yoshimori
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Mihara
authors.affiliation: Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan kanki@med.niigata-u.ac.jp.
authors.forename: Tomotake
authors.identifier: http://orcid.org/0000-0001-9646-5379
authors.initials: T
authors.lastname: Kanki
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000077543:Deferiprone; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008322:Mammals / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063306:Mitophagy / Q000187:drug effects; D008954:Models, Biological; D011728:Pyridones / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D059008:Time-Lapse Imaging
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D011728:Pyridones; D029701:Saccharomyces cerevisiae Proteins; D000077543:Deferiprone; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae; C110768:DNM1L protein, human; D034281:Dynamins