Details of a Researcher

Personnel Information

写真a

YAMANO KOJI

Job title

Associate Professor

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Campus Career 【 display / non-display 】

2022.04

　

　

Tokyo Medical and Dental University， Medical Research Institute， Pathophysiology， Department of Biomolecular Pathogenesis， Associate Professor
2022.05

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Now

Tokyo Medical and Dental University， Medical Research Institute， Division of Advanced Pathophysiological Science， Department of Biomolecular Pathogenesis， Associate Professor

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External Career 【 display / non-display 】

2014.09

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2017.03

Tokyo Metropolitan Institute of Medical Science,
2017.04

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2022.03

Tokyo Metropolitan Institute of Medical Science,
2022.04

-

Now

Tokyo Medical and Dental University, Medical Research Institute Pathophysiology, Associate Professor

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Research Areas 【 display / non-display 】

Cell biology

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Research Theme 【 display / non-display 】

Lifespan regulation of organelle component proteins, 2023.04 - 2028.03
Reconstitution of Parkin activation and recruitment to target membrane, 2018.04 - 2021.03

Summary： Mitochondrial quality control is an essential process to maintain cell homeostasis. Parkin and PINK1, gene products mutated in a genetic Parkinsonism play critical roles in ubiquitination of mitochondrial outer membrane proteins, which leads to elimination of damaged mitochondria via autophagy. In this study, I aimed to identify E2 enzymes for Parkin and reconstitute Parkin activation followed by membrane association. I identified several E2 enzymes that interact with activated Parkin and reconstituted Parkin-mediated ubiquitination reactions using isolated mitochondria. I also applied these methods for the discovery of novel interactions between OPTN, one of the autophagy adaptors, and ATG9A.
Molecular mechanism for activation of RBR-type E3 ubiquitin ligases, 2016.04 - 2018.03

Summary： E3 ligases transfer ubiquitin molecules to substrate proteins for their degradation. Molecular functions of RBR-type E3 ligases, however, largely remain unknown because their activities normally keep autoinhibited. Parkin is one of the RBR type E3 ligase that activates only on the dysfunctional mitochondria. In this study, I developed a method in which Parkin activation can be monitored in cultured cells through the interaction of E2 enzymes. E2 enzymes play a role in transferring ubiquitin molecule to E3 ligases and 40 different E2 enzymes are encoded in human genome. Using the method, I identified several E2 enzymes to interact with activated Parkin on the damaged mitochondria. Furthermore, this method also identified that one of the uncharacterized RBR-type E3 ligase forms several dot-like structures in the nucleus, and another RBR-type E3 ligase localizes on the lipid droplets.

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Published Papers & Misc 【 display / non-display 】

Yamano K, Kinefuchi H, Kojima W. Mitochondrial lipid dynamics regulated by MITOL-mediated ubiquitination. Journal of biochemistry. 2024.03; 175 (3): 217-219. ( PubMed, DOI )
Cui M, Yamano K, Yamamoto K, Yamamoto-Imoto H, Minami S, Yamamoto T, Matsui S, Kaminishi T, Shima T, Ogura M, Tsuchiya M, Nishino K, Layden BT, Kato H, Ogawa H, Oki S, Okada Y, Isaka Y, Kosako H, Matsuda N, Yoshimori T, Nakamura S. HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence. Proceedings of the National Academy of Sciences of the United States of America. 2024.01; 121 (2): e2306454120. ( PubMed, DOI )
Yamano K, Sawada M, Kikuchi R, Nagataki K, Kojima W, Endo R, Kinefuchi H, Sugihara A, Fujino T, Watanabe A, Tanaka K, Hayashi G, Murakami H, Matsuda N. Optineurin provides a mitophagy contact site for TBK1 activation. The EMBO journal. 2024.01; 43 (5): 754-779. ( PubMed, DOI )
Yamano K, Kinefuchi H, Kojima W. Mitochondrial quality control via organelle and protein degradation. Journal of biochemistry. 2023.12; ( PubMed, DOI )
Kurusu R, Fujimoto Y, Morishita H, Noshiro D, Takada S, Yamano K, Tanaka H, Arai R, Kageyama S, Funakoshi T, Komatsu-Hirota S, Taka H, Kazuno S, Miura Y, Koike M, Wakai T, Waguri S, Noda NN, Komatsu M. Integrated proteomics identifies p62-dependent selective autophagy of the supramolecular vault complex. Developmental cell. 2023.07; 58 (13): 1189-1205.e11. ( PubMed, DOI )
Hayashida R, Kikuchi R, Imai K, Kojima W, Yamada T, Iijima M, Sesaki H, Tanaka K, Matsuda N, Yamano K. Elucidation of ubiquitin-conjugating enzymes that interact with RBR-type ubiquitin ligases using a liquid-liquid phase separation-based method. The Journal of biological chemistry. 2023.02; 299 (2): 102822. ( PubMed, DOI )
Yamano K, Sawada M, Kikuchi R, Nagataki K, Kojima W, Sugihara A, Fujino T, Tanaka K, Hayashi G, Murakami H, Matsuda N. . Optineurin provides a mitophagy contact site for TBK1 activation bioRxiv. 2023.02;
Queliconi BB, Kojima W, Kimura M, Imai K, Udagawa C, Motono C, Hirokawa T, Tashiro S, Caaveiro JMM, Tsumoto K, Yamano K, Tanaka K, Matsuda N. Unfolding is the driving force for mitochondrial import and degradation of the Parkinson's disease-related protein DJ-1. Journal of cell science. 2021.11; 134 (22): ( PubMed, DOI )
Yamano K, Kojima W. Molecular functions of autophagy adaptors upon ubiquitin-driven mitophagy. Biochimica et biophysica acta. General subjects. 2021.10; 1865 (10): 129972. ( PubMed, DOI )
Kojima W, Yamano K, Kosako H, Imai K, Kikuchi R, Tanaka K, Matsuda N. Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy. Autophagy. 2021.08; 17 (8): 2011-2036. ( PubMed, DOI )
Onishi M, Yamano K, Sato M, Matsuda N, Okamoto K. Molecular mechanisms and physiological functions of mitophagy. The EMBO journal. 2021.02; 40 (3): e104705. ( PubMed, DOI )
Yamano K, Youle RJ. Two different axes CALCOCO2-RB1CC1 and OPTN-ATG9A initiate PRKN-mediated mitophagy. Autophagy. 2020.11; 16 (11): 2105-2107. ( PubMed, DOI )
Matsuda N, Yamano K. Two sides of a coin: Physiological significance and molecular mechanisms for damage-induced mitochondrial localization of PINK1 and Parkin. Neuroscience research. 2020.10; 159 16-24. ( PubMed, DOI )
Koyano F, Yamano K, Kosako H, Kimura Y, Kimura M, Fujiki Y, Tanaka K, Matsuda N. Parkin-mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes. EMBO reports. 2019.12; 20 (12): e47728. ( PubMed, DOI )
Koyano F, Yamano K, Kosako H, Tanaka K, Matsuda N. Parkin recruitment to impaired mitochondria for nonselective ubiquitylation is facilitated by MITOL. The Journal of biological chemistry. 2019.06; 294 (26): 10300-10314. ( PubMed, DOI )
Yamano K, Lazarou M. YoungMito 2018: Report on the 1st International Mitochondria Meeting for Young Scientists. Genes to cells : devoted to molecular & cellular mechanisms. 2018.10; 23 (10): 822-827. ( PubMed, DOI )
Okatsu K, Sato Y, Yamano K, Matsuda N, Negishi L, Takahashi A, Yamagata A, Goto-Ito S, Mishima M, Ito Y, Oka T, Tanaka K, Fukai S. Structural insights into ubiquitin phosphorylation by PINK1. Scientific reports. 2018.07; 8 (1): 10382. ( PubMed, DOI )
Yamano K, Wang C, Sarraf SA, Münch C, Kikuchi R, Noda NN, Hizukuri Y, Kanemaki MT, Harper W, Tanaka K, Matsuda N, Youle RJ. Endosomal Rab cycles regulate Parkin-mediated mitophagy. eLife. 2018.01; 7 ( PubMed, DOI )
Sato Y, Okatsu K, Saeki Y, Yamano K, Matsuda N, Kaiho A, Yamagata A, Goto-Ito S, Ishikawa M, Hashimoto Y, Tanaka K, Fukai S. Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30. Nature structural & molecular biology. 2017.11; 24 (11): 911-919. ( PubMed, DOI )
Matsuda N, Kimura M, Queliconi BB, Kojima W, Mishima M, Takagi K, Koyano F, Yamano K, Mizushima T, Ito Y, Tanaka K. Parkinson's disease-related DJ-1 functions in thiol quality control against aldehyde attack in vitro. Scientific reports. 2017.10; 7 (1): 12816. ( PubMed, DOI )
Izumikawa K, Nobe Y, Yoshikawa H, Ishikawa H, Miura Y, Nakayama H, Nonaka T, Hasegawa M, Egawa N, Inoue H, Nishikawa K, Yamano K, Simpson RJ, Taoka M, Yamauchi Y, Isobe T, Takahashi N. TDP-43 stabilises the processing intermediates of mitochondrial transcripts. Scientific reports. 2017.08; 7 (1): 7709. ( PubMed, DOI )
Unexpected mitochondrial matrix localization of Parkinson's disease-related DJ-1 mutants but not wild-type DJ-1 (vol 21, pg 772, 2016) 2017.01; 22 (1): 124. ( DOI )