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Integrated Biology Laboratories

Laboratory of Intracellular Membrane Dynamics

Prof. Tamotsu Yoshimori Prof. Tamotsu Yoshimori

Keyword:

Autophagy, Membrane traffic, Lysosome, Disease, Aging

Why do cells eat themselves?

Eukaryotic cells are equipped with the intracellular traffic network by witch a variety of macromolecules intercommunicate among organelles. The traffic is executed by dynamic membrane movement. so-called membrane traffic. We focus on autophagy, the membrane traffic delivering cargos from the cytoplasm to lysosomes for degradation, by using advanced methodologies of molecular cell biology, imaging, etc. Autophagy field is one of the hottest fields in life science. Prof Yoshimori in the lab has been leading the field together with Prof Ohsumi who received the 2016 Nobel Prize. He expanded Ohsumi’s breakthrough using yeast to mammalian, and has been leading autophagy field by elucidating molecular machinery and anti-diseases function of mammalian autophagy.

Fig1. The membrane dynamics of autophagy
Fig2. Autophagosome is engulfing the invading pathogenic bacteria (arrow). We reported for the first time that autophagy protects cells against pathogenic bacteria.

Members

Tamotsu Yoshimori (Professor) tamyoshi[at]fbs.osaka-u.ac.jp
Maho Hamasaki (Associate Professor) hamasaki[at]fbs.osaka-u.ac.jp
Shuhei Nakamura (Associate Professor, Institute for Advanced Co-Creation Studies) shuhei.nakamura[at]fbs.osaka-u.ac.jp
Keisuke Tabata (Assistant Professor) keisuke.tabata[at]fbs.osaka-u.ac.jp
Tatsuya Kaminishi (Assistant Professor, Graduate School of Medicine) tkaminishi[at]fbs.osaka-u.ac.jp
Akiko Kuma (Specially Appointed Associate Professor, Graduate School of Medicine) kuma[at]fbs.osaka-u.ac.jp
Hitomi Imoto (Specially Appointed Assistant Professor, Graduate School of Medicine) himoto[at]fbs.osaka-u.ac.jp
Satoshi Minami (Specially Appointed Assistant Professor, Graduate School of Medicine)  
Takayuki Shima (Specially Appointed Researcher, Graduate School of Medicine) tkshima[at]fbs
Eriko Ochi (Secretary, Graduate School of Medicine)  
Kayo Murata (Secretary, Graduate School of Medicine)  
Ayaka Tokumura (Technical Staff, Graduate School of Medicine)  
Akiko Nezu (Technical Staff, Graduate School of Medicine)  

You could probably reach more information of individual researchers by Research Map and researcher's search of Osaka-U.

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Q&A

What is your hot research topic?
We focus on the molecular mechanism of Autophagy and its correlation to some diseases and aging.
What kind of background do your lab members have?
Most of staffs have some expertise of Cell biology. In 2019 we got a new specialist for Structure Biology in our lab. Grad. Students are from a variety of area like faculty of Science (biology), Agriculture, Medicine, Pharmaceutical Sciences and Engineering.

Do you collaborate with institutions outside of Osaka Univ.?
We are in collaboration with lots of research institutes both within and outside of Japan. Specially, we have quite active international collaboration projects through HFSP Grant
(with USA, Germany Australia) and A3 Foresight program (with China and Korea).
How do you develop your research?
We will continue our detailed analysis of molecular function in mammalian autophagy. We also will promote the incorporation of our research results into real-life applications. To this end, we recently started a venture named "AutophagyGo".

Research Highlights

Publications (Research Articles, Reviews, Books)

2020

Ikari S, Lu SL, Hao F, Imai K, Araki Y, Yamamoto Y, Tsai CY, Nishiyama Y, Shitan N, Yoshimori T, Otomo T, Noda T

Starvation-induced autophagy via calcium-dependent TFEB dephosphorylation is suppressed by Shigyakusan.

PLoS One 15(3):e0230156  2020 PMID:32134989 DOI:10.1371/journal.pone.0230156

Matsuda J, Takahashi A, Takabatake Y, Sakai S, Minami S, Yamamoto T, Fujimura R, Namba-Hamano T, Yonishi H, Nakamura J, Kimura T, Kaimori JY, Matsui I, Takahashi M, Nakao M, Izumi Y, Bamba T, Matsusaka T, Niimura F, Yanagita M, Yoshimori T, Isaka Y

Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.

Autophagy 1月16日  2020 PMID:31944172 DOI:10.1080/15548627.2020.1712107

2019

Nakashima A, Cheng SB, Ikawa M, Yoshimori T, Huber WJ, Menon R, Huang Z, Fierce J, Padbury JF, Sadovsky Y, Saito S, Sharma S

Evidence for lysosomal biogenesis proteome defect and impaired autophagy in preeclampsia.

Autophagy 1月15日  2019 PMID:31856641 DOI:10.1080/15548627.2019.1707494

Unno R, Kawabata T, Taguchi K, Sugino T, Hamamoto S, Ando R, Okada A, Kohri K, Yoshimori T, Yasui T

Deregulated MTOR (mechanistic target of rapamycin kinase) is responsible for autophagy defects exacerbating kidney stone development

Autophagy 1月15日  2019 PMID:31257986 DOI:10.1080/15548627.2019.1635382

Lee JH, Rao MV, Yang DS, Stavrides P, Im E, Pensalfini A, Huo C, Sarkar P, Yoshimori T, Nixon RA

Transgenic expression of a ratiometric autophagy probe specifically in neurons enables the interrogation of brain autophagy in vivo

Autophagy 15(3):543-557  2019 PMID:30269645 DOI:10.1080/15548627.2018.1528812

Lystad AH, Carlsson SR, de la Ballina LR, Kauffman KJ, Nag S, Yoshimori T, Melia TJ, Simonsen A

Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes

Nat. Cell Biol. 21(3):372-383  2019 PMID:30778222 DOI:10.1038/s41556-019-0274-9

Nakamura S, Oba M, Suzuki M, Takahashi A, Yamamuro T, Fujiwara M, Ikenaka K, Minami S, Tabata N, Yamamoto K, Kubo S, Tokumura A, Akamatsu K, Miyazaki Y, Kawabata T, Hamasaki M, Fukui K, Sango K, Watanabe Y, Takabatake Y, Kitajima TS, Okada Y, Mochizuki H, Isaka Y, Antebi A, Yoshimori T

Suppression of autophagic activity by Rubicon is a signature of aging

Nat. Commun. 10(1):847  2019 PMID:30783089 DOI:10.1038/s41467-019-08729-6

Chang C, Young LN, Morris KL, von Bülow S, Schöneberg J, Yamamoto-Imoto H, Oe Y, Yamamoto K, Nakamura S, Stjepanovic G, Hummer G, Yoshimori T, Hurley JH

Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics

Mol. Cell 73(2):339-353  2019 PMID:30581147 DOI:10.1016/j.molcel.2018.10.035

2018

Tan JM, Mellouk N, Osborne SE, Ammendolia DA, Dyer DN, Li R, Brunen D, van Rijn JM, Huang J, Czuczman MA, Cemma MA, Won AM, Yip CM, Xavier RJ, MacDuff DA, Reggiori F, Debnath J, Yoshimori T, Kim PK, Fairn GD, Coyaud E, Raught B, Muise AM, Higgins DE, Brumell JH

An ATG16L1-dependent pathway promotes plasma membrane repair and limits Listeria monocytogenes cell-to-cell spread

NAT. MICROBIOL 3(12):1472_1485  2018 PMID:30478389 DOI:10.1038/s41564-018-0293-5

Mori H, Fukuhara T, Ono C, Tamura T, Sato A, Fauzyah Y, Wada M, Okamoto T, Noda T, Yoshimori T, Matsuura Y

Induction of selective autophagy in cells replicating hepatitis C virus genome

J. Gen. Virol. 99(12):1643-1657  2018 PMID:30311874 DOI:10.1099/jgv.0.001161

Lee JH, Rao MV, Yang DS, Stavrides P, Im E, Pensalfini A, Huo C, Sarkar P, Yoshimori T, Nixon RA

Transgenic expression of a ratiometric autophagy probe specifically in neurons enables the interrogation of brain autophagy in vivo. Autophagy

Autophagy 15(3):543-557  2018 PMID:30269645 DOI:10.1080/15548627.2018.1528812

Aoki A, Nakashima A, Kusabiraki T, Ono Y, Yoshino O, Muto M, Kumasawa K, Yoshimori T, Ikawa M, Saito S

Trophoblast-Specific Conditional Atg7 Knockout Mice Develop Gestational Hypertension.

Am. J. Pathol. 188(11):2474-2486  2018 PMID:30165042 DOI:10.1016/j.ajpath.2018.07.021

Itoh K, Adachi Y, Yamada T, Suzuki TL, Otomo T, McBride HM, Yoshimori T, Iijima M, Sesaki H

A brain-enriched Drp1 isoform associates with lysosomes, late endosomes and the plasma membrane.

J. Biol. Chem. 293(30):11809-11822  2018 PMID:29853636 DOI:10.1074/jbc.RA117.001253

Saita S, Tatsuta T, Lampe PA, König T, Ohba Y, Langer T

PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria.

Embo J. 37(4):e97909  2018 PMID:29301859 DOI:10.15252/embj.201797909

Yang F, Yang L, Wataya-Kaneda M, Hasegawa J, Yoshimori T, Tanemura A, Tsuruta D, Katayama I

Dysregulation of autophagy in melanocytes contributes to hypopigmented macules in tuberous sclerosis complex.

J. Dermatol. Sci. 89(2):155-164  2018 PMID:29146131 DOI:10.1016/j.jdermsci.2017.11.002

Nakamura S, Yoshimori T

Autophagy and Longevity.

Mol. Cells 41(1):65-72  2018 PMID:29370695 DOI:10.14348/molcells.2018.2333

2017

Vukotic M, Nolte H, Konig T, Saita S, Ananjew M, Kruger M, Tatsuta T, Langer T

Acylglycerol Kinase Mutated in Sengers Syndrome Is a Subunit of the TIM22 Protein Translocase in Mitochondria.

Mol. Cell 67(3)471-483  2017 PMID:28712724 DOI:10.1016/j.molcel.2017.06.013

Lorenzo Galluzzi, Eric H Baehrecke, Andrea Ballabio, Patricia Boya, José Manuel Bravo‐San Pedro, Francesco Cecconi, Augustine M Choi, Charleen T Chu, Patrice Codogno, Maria Isabel Colombo, Ana Maria Cuervo, Jayanta Debnath, Vojo Deretic, Ivan Dikic, Eeva‐Liisa Eskelinen, Gian Maria Fimia, Simone Fulda, David A Gewirtz, Douglas R Green, Malene Hansen, J Wade Harper, Marja Jäättelä, Terje Johansen,Gabor Juhasz, Alec C Kimmelman,Claudine Kraft, Nicholas T Ktistakis, Sharad Kumar, Beth Levine, Carlos Lopez‐Otin, Frank Madeo, Sascha Martens, Jennifer Martinez, Alicia Melendez, Noboru Mizushima, Christian Münz, Leon O Murphy, Josef M Penninger, Mauro Piacentini, Fulvio Reggiori, David C Rubinsztein, Kevin M Ryan, Laura Santambrogio, Luca Scorrano, Anna Katharina Simon, Hans‐Uwe Simon, Anne Simonsen, Nektarios Tavernarakis, Sharon A Tooze, Tamotsu Yoshimori, Junying Yuan, Zhenyu Yue,Qing Zhong, Guido Kroemer

Molecular definitions of autophagy and related processes

Embo J. 36(13):1811-1836  2017 PMID:28596378 DOI:10.15252/embj.201796697

Tomonori Kimura, Yoshitaka Isaka, Tamotsu Yoshimori

Autophagy and kidney inflammation

Autophagy 13(6):997-1003  2017 PMID:28441075 DOI:10.1080/15548627.2017.1309485

Yukiko Yoshida, Sayaka Yasuda, Toshiharu Fujita, Maho Hamasaki, Arisa Murakami, Junko Kawawaki, Kazuhiro Iwai, Yasushi Saeki, Tamotsu Yoshimori, Noriyuki Matsuda, Keiji Tanaka

Ubiquitination of exposed glycoproteins by SCFFBXO27 directs damaged lysosomes for autophagy

Proc. Natl. Acad. Sci. U. S. A. 114(32):8574-8579  2017 PMID:28743755 DOI:10.1073/pnas.1702615114

Varnesh Tiku, Chirag Jain, Yotam Raz, Shuhei Nakamura, Bree Heestand, Wei Liu, Martin Späth, H. Eka. D. Suchiman, Roman-Ulrich Müller, P. Eline Slagboom, Linda Partridge, Adam Antebi

Small nucleoli are a cellular hallmark of longevity

Nat. Commun. 8:16083  2017 PMID:28853436 DOI:10.1038/ncomms16083

Miwa Sasai, Naoya Sakaguchi, Ji Su Ma, Shuhei Nakamura, Tsuyoshi Kawabata, Hironori Bando, Youngae Lee, Tatsuya Saitoh, Shizuo Akira, Akiko Iwasaki, Daron M Standley, Tamotsu Yoshimori, Masahiro Yamamoto

Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense

Nat. Immunol. 18(8):899-910  2017 PMID:28604719 DOI:10.1038/ni.3767

Ikumi Hori, Takanobu Otomo, Mitsuko Nakashima, Fuyuki Miya, Yutaka Negishi, Hideaki Shiraishi, Yutaka Nonoda, Shinichi Magara, Jun Tohyama, Nobuhiko Okamoto, Takeshi Kumagai, Konomi Shimoda, Yoshiya Yukitake, Daigo Kajikawa, Tomohiro Morio, Ayako Hattori, Motoo Nakagawa, Naoki Ando, Ichizo Nishino, Mitsuhiro Kato, Tatsuhiko Tsunoda, Hirotomo Saitsu, Yonehiro Kanemura, Mami Yamasaki, Kenjiro Kosaki, Naomichi Matsumoto, Tamotsu Yoshimori, Shinji Saitoh

Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement

Sci Rep 7(1):3552  2017 PMID:28615637 DOI:10.1038/s41598-017-02840-8

Atsushi Takahashi, Yoshitsugu Takabatake, Tomonori Kimura, Ikuko Maejima, Tomoko Namba, Takeshi Yamamoto, Jun Matsuda, Satoshi Minami, Jun-ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Tamotsu Yoshimori and Yoshitaka Isaka

Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules

Diabetes 66(5):1359-1372  2017 PMID:28246295 DOI:10.2337/db16-0397

Shiou-Ling Lu, Tsuyoshi Kawabata, Yi-Lin Cheng, Hiroko Omori, Maho Hamasaki, Tatsuya Kusaba, Ryo Iwamoto, Hirokazu Arimoto, Takeshi Noda, Yee-Shin Lin, Tamotsu Yoshimori

Endothelial cells are intrinsically defective in xenophagy of Streptococcus pyogenes

PLoS Pathog. 13(7):e1006444  2017 PMID:28683091 DOI:10.1371/journal.ppat.1006444

Hubber A, Kubori T, Coban C, Matsuzawa T, Ogawa M, Kawabata T, Yoshimori T, Nagai H

Bacterial secretion system skews the fate of Legionella-containing vacuoles towards LC3-associated phagocytosis.

Sci Rep 7:44795  2017 PMID:28317932 DOI:10.1038/srep44795

Nishiumi F, Ogawa M, Nakura Y, Hamada Y, Nakayama M, Mitobe J, Hiraide A, Sakai N, Takeuchi M, Yoshimori T, Yanagihara I

Intracellular fate of Ureaplasma parvum entrapped by host cellular autophagy.

MicrobiologyOpen 6(3):e00441  2017 PMID:28088841 DOI:10.1002/mbo3.441

Kondo H, Maksimova N, Otomo T, Kato H, Imai A, Asano Y, Kobayashi K, Nojima S, Nakaya A, Hamada Y, Irahara K, Gurinova E, Sukhomyasova A, Nogovicina A, Savvina M, Yoshimori T, Ozono K Sakai N

Mutation in VPS33A affects metabolism of glycosaminoglycans: a new type of mucopolysaccharidosis with severe systemic symptoms.

Hum. Mol. Genet. 26(1):173-183  2017 PMID:28013294 DOI:10.1093/hmg/ddw377

Nakamura S, Yoshimori T

New insights into autophagosome-lysosome fusion.

J. Cell Sci. 130(7):1209-1216  2017 PMID:28302910 DOI:10.1242/jcs.196352

2016

Toshiya Nishimura, Shuhei Nakamura, Minoru Tanaka

A Structurally and Functionally Common Unit in Testes and Ovaries of Medaka

Sex. Dev. 10:159-165  2016 PMID:27410401 DOI:10.1159/000447313

Dan Wang, Lei Hou, Shuhei Nakamura, Ming Su, Fang Li, Weiyang Chen, Yizhen Yan, Christopher D. Green, Di Chen, Hong Zhang, Adam Antebi, Jing‐Dong J. Han

LIN-28 balances longevity and germline stem cell number in Caenorhabditis elegans through let-7/AKT/DAF-16 axis

Aging Cell 16(1):113-124  2016 PMID:27730721 DOI:10.1111/acel.12539

Nakamura S, Hasegawa J, Yoshimori T

Regulation of lysosomal phosphoinositide balance by INPP5E is essential for autophagosome-lysosome fusion.

Autophagy 12(12):2500-2501  2016 PMID:27715391 DOI:10.1080/15548627.2016.1234568

Tanaka S, Hikita H, Tatsumi T, Sakamori R, Nozaki Y, Sakane S Shiode Y, Nakabori T, Saito Y, Hiramatsu N, Tabata K, Kawabata T, Hamasaki M, Eguchi H, Nagano H, Yoshimori T, Takehara T

Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease.

Hepatology 64(6):1994-2014  2016 PMID:27637015 DOI:10.1002/hep.28820

Imai K, Hao F, Fujita N, Tsuji Y, Oe Y, Araki Y, Hamasaki M, Noda T, Yoshimori T

Atg9A Trafficking Through the Recycling Endosomes is Required for Autophagosome Formation.

J. Cell Sci. 129(20):3781-3791  2016 PMID:27587839 DOI:10.1242/jcs.196196

Hasegawa J, Iwamoto R, Otomo T, Nezu A, Hamasaki M, Yoshimori T

Autophagosome-lysosome fusion in neurons requires INPP5E, a protein associated with Joubert syndrome

Embo J. 35(17):1853-67  2016 PMID:27340123 DOI:10.15252/embj.201593148

Ideal Candidate (To Graduate Student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.

Contact

Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University,
2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL: +81-6-6879-3588

E-mail: tamyoshi[at]fbs.osaka-u.ac.jp (Prof. Tamotsu Yoshimori)

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PAGETOP