A02：The relationship between iron homeostasis and pathogenesis
Yoshihito KISHITA
（Department of Life Science,
Faculty of Science and Engineering, Kindai University）
Lab website
Iron (Fe), copper (Cu), and zinc (Zn) are the main biometals in mitochondria. Fe plays the most important role and is essential for the function of the mitochondrial respiratory chain complex. Heme and iron-sulfur clusters are synthesized mainly in mitochondria and incorporated into components of the mitochondrial respiratory chain complex. Abnormal mitochondrial iron homeostasis has been reported to impair respiratory chain complex function and cause mitochondrial disease. Through large-scale and comprehensive genomic analysis of patients with mitochondrial diseases, we have identified several genes involved in mitochondrial iron-sulfur cluster formation and heme synthesis. However, the relationship between iron-sulfur clusters and heme in the development and progression of disease is not clear. In this study, we will clarify the molecular mechanisms that an imbalance between mitochondrial iron-sulfur clusters formation and heme synthesis causes disease.
Major publications
M. Shimura, N. Nozawa N, M. Ogawa-Tominag, T. Fushimi, M. Tajika, K. Ichimoto, A. Matsunaga, T. Tsuruoka, Y. Kishita, T. Ishii, K. Takahashi, T. Tanaka, M. Nakajima, Y. Okazaki, A. Ohtake, K. Murayama K
“Effects of 5-aminolevulinic acid and sodium ferrous citrate on fibroblasts from individuals with mitochondrial diseases”
Sci Rep 2019, 9, 10549
doi: 10.1038/s41598-019-46772-x
A. Imai-Okazaki, Y. Kishita, M. Kohda, Y. Mizuno, T. Fushimi, A. Matsunaga, Y. Yatsuka, T. Hirata, H. Harashima, A. Takeda, A. Nakaya, Y. Sakata, S. Kogaki, A. Ohtake, K. Murayama, Okazaki Y
“Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background”
Int J Cardiol 2019, 279, 115-121
doi: 10.1016/j.ijcard.2019.01.017
E. Ogawa, M. Shimura, T. Fushimi, M. Tajika, K. Ichimoto, A. Matsunaga, T. Tsuruoka, M. Ishige, T. Fuchigami, T. Yamazaki, M. Mori, M. Kohda, Y. Kishita, Y. Okazaki, S. Takahashi, A. Ohtake, K. Murayama
“Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients”
J Inherit Metab Dis 2017, 40, 685-693
doi: 10.1007/s10545-017-0042-6
M. Kohda, Y. Tokuzawa, Y. Kishita, H. Nyuzuki, Y. Moriyama, Y. Mizuno, T. Hirata, Y. Yatsuka, Y. Yamashita-Sugahara, Y. Nakachi, H. Kato, A. Okuda, S. Tamaru, NN. Borna, K. Banshoya, T. Aigaki, Y. Sato-Miyata, K. Ohnuma, T. Suzuki, A. Nagao, H. Maehata, F. Matsuda, K. Higasa, M. Nagasaki, J. Yasuda, M. Yamamoto, T. Fushimi, M. Shimura, K. Kaiho-Ichimoto, H. Harashima, T. Yamazaki, M. Mori, K. Murayama, A. Ohtake, Y. Okazaki
“A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies”
PLOS Genet 2016, 12, e1005679
doi: 10.1371/journal.pgen.1005679
Y. Kishita Y, A. Pajak, NA. Bolar, CM. Marobbio, C. Maffezzini, DV. Miniero, M. Monné, M. Kohda, H. Stranneheim, K. Murayama, K. Naess, N. Lesko, H. Bruhn, A. Mourier, R. Wibom, I. Nennesmo, A. Jespers, P. Govaert, A. Ohtake, L. Van Laer, BL. Loeys, C. Freyer, F. Palmieri, A. Wredenberg, Y. Okazaki, A. Wedell
“Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26”
Am J Hum Genet 2015, 97, 761-8
doi: 10.1016/j.ajhg.2015.09.013