TY - JOUR
T1 - Onsite GTP fuelling via DYNAMO1 drives division of mitochondria and peroxisomes
AU - Imoto, Yuuta
AU - Abe, Yuichi
AU - Honsho, Masanori
AU - Okumoto, Kanji
AU - Ohnuma, Mio
AU - Kuroiwa, Haruko
AU - Kuroiwa, Tsuneyoshi
AU - Fujiki, Yukio
N1 - Funding Information:
This work was supported in part by grants from Japan Society for the Promotion of Science Fellowships (no. 14J04556 to Y.I.), MEXT-Supported Program for the Strategic Research Foundation at Private Universities (no. JWU2014-1018 to T.K.), Core Research for Evolutional Science and Technology (CREST) Program of Japan Science and Technology Agency (JST) (to T.K.), Ministry of Education, Culture, Sports, Science, and Technology of Japan, Grants-in-Aid for Scientific Research (no. 17K00676 to M.O.; no. JP16H04813 to T.K; nos. JP24247038, JP25112518, JP25116717, JP26116007, JP15K14511, and JP15K21743 to Y.F.), and grants from the Takeda Science Foundation (to Y.F.), Naito Foundation (to Y.F.) and Japan Foundation for Applied Enzymology and Novartis Foundation (Japan) for the Promotion of Science (to Y.F.). We thank O. Misumi (Yamaguchi University) and F. Yagisawa (Ryukyu University) for C. merolae 10D, Y. Toh (Kyushi University) for supporting electron microscope, and M. Matsumoto (Human Proteome Research Centre, Kyushu University) for LC–MS/MS proteomic analysis and instructive comments, M. Ishii and K. Shimizu (Kyushu University) for generous support to prepare manuscript, K. Itoh (Johns Hopkins University) for discussion and generous support for the research. We also thank S. R. Doctrow and M. Arico for helpful comments.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Mitochondria and peroxisomes proliferate by division. During division, a part of their membrane is pinched off by constriction of the ring-shaped mitochondrial division (MD) and peroxisome-dividing (POD) machinery. This constriction is mediated by a dynamin-like GTPase Dnm1 that requires a large amount of GTP as an energy source. Here, via proteomics of the isolated division machinery, we show that the 17-kDa nucleoside diphosphate kinase-like protein, dynamin-based ring motive-force organizer 1 (DYNAMO1), locally generates GTP in MD and POD machineries. DYNAMO1 is widely conserved among eukaryotes and colocalizes with Dnm1 on the division machineries. DYNAMO1 converts ATP to GTP, and disruption of its activity impairs mitochondrial and peroxisomal fissions. DYNAMO1 forms a ring-shaped complex with Dnm1 and increases the magnitude of the constricting force. Our results identify DYNAMO1 as an essential component of MD and POD machineries, suggesting that local GTP generation in Dnm1-based machinery regulates motive force for membrane severance.
AB - Mitochondria and peroxisomes proliferate by division. During division, a part of their membrane is pinched off by constriction of the ring-shaped mitochondrial division (MD) and peroxisome-dividing (POD) machinery. This constriction is mediated by a dynamin-like GTPase Dnm1 that requires a large amount of GTP as an energy source. Here, via proteomics of the isolated division machinery, we show that the 17-kDa nucleoside diphosphate kinase-like protein, dynamin-based ring motive-force organizer 1 (DYNAMO1), locally generates GTP in MD and POD machineries. DYNAMO1 is widely conserved among eukaryotes and colocalizes with Dnm1 on the division machineries. DYNAMO1 converts ATP to GTP, and disruption of its activity impairs mitochondrial and peroxisomal fissions. DYNAMO1 forms a ring-shaped complex with Dnm1 and increases the magnitude of the constricting force. Our results identify DYNAMO1 as an essential component of MD and POD machineries, suggesting that local GTP generation in Dnm1-based machinery regulates motive force for membrane severance.
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U2 - 10.1038/s41467-018-07009-z
DO - 10.1038/s41467-018-07009-z
M3 - Article
C2 - 30401830
AN - SCOPUS:85056093849
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4634
ER -