Laboratory for Metabolic Networks

PUBLICATIONS

 

1.   Takeuchi T, Kubota T, Nakanishi Y, Tsugawa H, Suda W, Kwon AT, Yazaki J, Ikeda K, Nemoto S, Mochizuki Y, Kitami T, Yugi K, Mizuno Y, Yamamichi N, Yamazaki T, Takamoto I, Kubota N, Kadowaki T, Arner E, Carninci P, Ohara O, Arita M, Hattori M, Koyasu S, Ohno H. 2023. Gut microbiota carbohydrate metabolism contributes to insulin resistance. Nature 621: 389-395. [Journal]

 

 

2.   Kobayashi A, Azuma K, Takeiwa T, Kitami T, Horie K, Ikeda K, Inoue S. FRET-based respirasome assembly screen defines potential therapeutic intervention that improves muscle mitochondrial respiration and exercise performance. 2023. Nature Communications 14: 312. [Journal]

 

 

3.  Takeuchi T, Miyauchi E, Kanaya T, Kato T, Nakanishi Y, Watanabe T, Kitami T, Taida T, Sasaki T, Negishi H, Shimamoto S, Matsuyama A, Kimura I, Williams IR, Ohara O, Ohno H. 2021. Acetate differentially regulates IgA reactivity to commensal bacteria. Nature 595: 560-564.  [PubMed] [Journal]

 

 

4.   Mencke P, Boussaad I, Romano CD, Kitami T, Linster CL, Krüger R. 2021. The role of DJ-1 in cellular metabolism and pathophysiological implications for Parkinson's disease. Cells 10(2):347. [Journal]

 

 

5.   Kitami T, Fukuda S (co-first), Kato T  (co-first), Yamaguti K, Nakatomi Y, Yamano E, Kataoka Y, Mizuno K, Tsuboi Y, Kogo Y, Suzuki H, Itoh M, Morioka MS, Kawaji H, Koseki H, Kikuchi J, Hayashizaki Y, Ohno H, Kuratsune H, Watanabe Y. 2020. Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population. Scientific Reports 10:19933. [Journal]

 

 

6.   Tran UT & Kitami T (corresponding). 2019. Niclosamide activates the NLRP3 inflammasome by intracellular acidification and mitochondrial inhibition. Communications Biology 2:2. [Journal]

 

Why it's important: This was our first attempt in appliying chemical screens to understand the role of mitochondria in inflammatory pathway. We used combinatorial screening approach to understand how a drug called niclosamide activates inflammatory pathway. Surprisingly, we find that this drug is able to engage two different targets at once, blocking both glycolytic and mitochondrial ATP production, which leads to loss of potassium gradient and inflammatory cell death.

 

 

7.   Kaji T, Hijikata A, Ishige A, Kitami T, Watanabe T, Ohara O, Yanaka N, Okada M, Shimoda M, Taniguchi M, Takemori T. 2016. CD4 memory T cells develop and acquire functional competence by sequential cognate interactions and stepwise gene regulation. International Immunology 28: 267-82. [PubMed] [Journal]

 

 

8.   Sancak Y, Markhard AL, Kitami T, Kovács-Bogdán E, Kamer KJ, Udeshi ND, Carr SA, Chaudhuri D, Clapham DE, Li AA, Calvo SE, Goldberger O, Mootha VK. 2013. EMRE is an essential component of the mitochondrial calcium uniporter complex. Science 342: 1379-82. [PubMed] [Journal]

 

 

9.   Kitami T, Logan DJ, Negri J, Hasaka T, Tolliday NJ, Carpenter AE, Spiegelman BM, Mootha VK. 2012. A chemical screen probing the relationship between mitochondrial content and cell size.  PLoS ONE 7(3) e33755. [Journal]

 

Why it's important: We tried to look for chemicals that can increase the amount of mitochondria in the cell (a process called mitochondrial biogenesis) as potential therapeutics for mitochondria-related diseases. However, even after screening 30,000 chemicals, we found that most of them just ended up making the cells bigger! Interestingly, we rediscovered an observation made over 40 years ago that mitochondrial content changes in proportion to cell size [Posakony et al. 1977].

 

 

10.   Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB, Mootha VK. 2012. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336: 1040-1044. [PubMed] [Journal]

 

 

11.   Wagner BK*, Kitami T* (co-first), Gilbert TJ, Peck D, Ramanathan A, Schreiber SL, Golub TR, Mootha VK. 2008. Large-scale chemical dissection of mitochondrial function. Nature Biotechnology 26: 343-351. [PubMed] [Journal]

 

Why it's important: We find that many of the mitochondrial assays (ATP, mitochondrial membrane potential, MTT, ROS, etc.) are not the same (this point is also nicely highlighted by others) when we perform these assays in parallel across thousands of chemicals. When we take advantage of these differences, we can uncover new drug toxicity, new drug target, and new properties of mitochondria through data-mining.