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Biomolecular Networks Laboratories

Laboratory of Mitochondrial Dynamics

Assoc. Prof. OKAMOTO Koji Assoc. Prof. OKAMOTO Koji

Keywords:

Yeast, Mitochondria, Organelle, Mitophagy

Unraveling mitochondrial quality and quantity control mechanisms

Mitochondria are energy-converting organelles that act as "the power plants of the cell", and change their quantity in response to cellular energy demand. They also accumulate oxidative stress from reactive oxygen species generated during electron transport, and damaged mitochondria are selectively eliminated from the cytoplasm. These quality and quantity control systems involve mitochondria-specific autophagy (mitophagy), and numerous studies suggest that defects in these systems are associated with various human diseases. Mitophagy is a catabolic process conserved from yeast to humans that sequesters and degrades mitochondria as whole organelles. The aim of our study is to uncover the general principle of mitophagy at the molecular and cellular levels, and elucidate the physiological function of this degradation process as an intracellular quality and quantity control system.

The landmark protein Atg32 is induced in response to oxidative stress, and localized on the surface of mitochondria to recruit Atg8 and Atg11, two proteins critical for cargo recognition. Atg11 acts as a scaffold for assembly of other Atg proteins that cooperatively mediate formation of isolation membranes surrounding mitochondria.

Members

Koji Okamoto (Associate Professor) kokamoto[at]fbs.osaka-u.ac.jp
Mashun Onishi (JSPS Postdoctoral Fellow) mashun07[at]fbs.osaka-u.ac.jp
Ramona Schuster (JSPS Postdoctoral Fellowships for Research in Japan) ramonaschuster[at]fbs.osaka-u.ac.jp
LIU Yang(D4)  
Kanako Fujii(D2)      
Ritsu Shibata(D2) rshibata[at]fbs.osaka-u.ac.jp
Duan Lan(D1)  
Mitsutaka Kubota(D1) kubota98[at]fbs.osaka-u.ac.jp
Yuko Imada (Secretary) yimada[at]fbs.osaka-u.ac.jp

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?
Previous studies suggest that mitochondria are established independently of other organelles. However, it has recently become evident that they cooperate phyisically and functionally with other organelles suvh as the endoplasmic reticulum (ER), peroxisome, and lysosome. We found that selective degradation of mitochondria is also regulated via ER-localized proteins, and are now analyzing its molecular mechanisms.
What is your breakthrough or research progress in the last 5 years?
We have revealed that selective degradation of mitochondria is intimately linked to diverse processes including phospholipid methylation, protein N-terminal acetylation, phospholipid dephospholylation, nutrient/stress signaling, ER-associated degradation, and ER membrane protein insertion.
What kind of background do your lab members have?
The lab members have expertise on molecular biology, biochemistry, genetics, and cell biology using becteria, yeast, mammalian cultured cells as model systems.
Do you collaborate with institutions outside of Osaka Univ.?
We are currently collaborating with researchers from Wakayama University, Nagoya City University, Johns Hopkins University (Baltimore, MA, USA), and University of Groningen (Groningen, Netherlands).
What kind of careers do your Lab's alumni go on to?
Six former lab members are now working at companies, taking a postdoc in Germany, and stadying at the graduate school in the USA.
How do you develop your research?
We anticipate to decipher basic principles underlying selective degradation of mitochondria at the molecular level in depth. Recently, using yeast, we have established a label-free method to detect selective degradation of mitochondria. We aim to apply this method to a variety of organisms except for model systems in the laboratories, and elucidate the universality and diversity in selective degradation of mitochondria.

Research Highlights

Publications (Research Articles, Reviews, Books)

2020

Calvellia H, Krigman J, Onishi M, Narendra DP, Sun N, Okamoto K.

Detection of mitophagy in mammalian cells, mice, and yeast.

Methods Cell Biol. 155: 557-579  2020 PMID:32183977 DOI:10.1016/bs.mcb.2019.10.006

2019

Morita K, Matsuda F, Okamoto K, Ishii J, Kondo A, Shimizu H.

Repression of mitochondrial metabolism for cytosolic pyruvate-derived chemical production in Saccharomyces cerevisiae.

Microb. Cell. Fact. 0.872916667  2019 PMID:31615527 DOI:10.1186/s12934-019-1226-6

Zheng L, Shu WJ, Li YM, Mari M, Yan C, Wang D, Yin ZH, Jiang W, Zhou Y,_Okamoto K, Reggiori F, Klionsky DJ, Song Z, Du HN.

The Paf1 complex transcriptionally regulates the mitochondrial-anchored protein Atg32 leading to activation of_mitophagy.

Autophagy 1月14日  2019 PMID:31525119 DOI:10.1080/15548627.2019.1668228

Murakawa T, Okamoto K, Omiya S, Taneike M, Yamaguchi O, Otsu K

A Mammalian Mitophagy Receptor, Bcl2-L-13, Recruits the ULK1 Complex to Induce Mitophagy.

Cell Reports 26: 338-345.e6  2019 PMID:30625316 DOI:10.1016/j.celrep.2018.12.050

2018

Yamada T, Murata D, Adachi Y, Itoh K, Kameoka S, Igarashi A, Kato T, Araki Y, Huganir RL, Dawson TM, Yanagawa T, Okamoto K, Iijima M, Sesaki H

Mitochondrial Stasis Reveals p62-Mediated Ubiquitination in Parkin-Independent Mitophagy and Mitigates Nonalcoholic Fatty Liver Disease

Cell Metab. 28: 588-604  2018 PMID:30017357 DOI:10.1016/j.cmet.2018.06.014

Liu Y, Okamoto K

The TORC1 signaling pathway regulates respiration-induced mitophagy in yeast

Biochem. Biophys. Res. Commun. 502: 76-83  2018 PMID:29787763 DOI:10.1016/j.bbrc.2018.05.123

Onishi M, Nagumo N, Iwashita S, Okamoto K

The ER membrane insertase Get1/2 is required for efficient mitophagy in yeast

Biochem. Biophys. Res. Commun. 503: 14-20  2018 PMID:29673596 DOI:10.1016/j.bbrc.2018.04.114

Xu X, Okamoto K

The Nem1-Spo7 protein phosphatase complex is required for efficient mitophagy in yeast

Biochem. Biophys. Res. Commun. 496: 51-57  2018 PMID:29305265 DOI:10.1016/j.bbrc.2017.12.163

2017

Kameoka S, Adachi Y, Okamoto K, Iijima M, Sesaki H

Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics

Trends Cell Biol. 28: 67-76  2017 PMID:28911913 DOI:10.1016/j.tcb.2017.08.011

Nagumo S, Okamoto K

Investigation of yeast mitophagy with fluorescence microscopy and Western blotting

Methods in Molecular Biology 1759: 71-83  2017 PMID:28337707 DOI:10.1007/7651_2017_11

Eiyama A, Okamoto K

Assays for mitophagy in yeast

Methods in Molecular Biology 1567:337-347.   2017 PMID:28276028 DOI:10.1007/978-1-4939-6824-4_20

Our ideal candidate (as a 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 Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University,
1-3 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL: +81-6-6879-7970

E-mail: kokamoto[at]fbs.osaka-u.ac.jp (Assoc. Prof. Koji Okamoto)

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