Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division

International Journal of Molecular Sciences

Yuuta Imoto¹  Hanna Mandel²  Tzipora C. Falik-Zaccai²  Zee-Fen Chang³  Masanori Honsho⁴  Yuichi Abe⁴  Yukio Fujiki⁴ 

[1]Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA

[2]Galilee Medical Center, Institute of Human Genetics, Nahariya 22100, Israel

[3]Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan

[4]Medical Institute of Bioregulation, Institute of Rheological Functions of Food—Kyushu University Collaboration Program, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan

关键词: peroxisome;    constriction;    NDP kinase;    GTP;    nme3 patient;   

DOI  :  10.3390/ijms21218040

来源: DOAJ

【 摘 要 】

Peroxisomes proliferate by sequential processes comprising elongation, constriction, and scission of peroxisomal membrane. It is known that the constriction step is mediated by a GTPase named dynamin-like protein 1 (DLP1) upon efficient loading of GTP. However, mechanism of fuelling GTP to DLP1 remains unknown in mammals. We earlier show that nucleoside diphosphate (NDP) kinase-like protein, termed dynamin-based ring motive-force organizer 1 (DYNAMO1), generates GTP for DLP1 in a red alga, Cyanidioschyzon merolae. In the present study, we identified that nucleoside diphosphate kinase 3 (NME3), a mammalian homologue of DYNAMO1, localizes to peroxisomes. Elongated peroxisomes were observed in cells with suppressed expression of NME3 and fibroblasts from a patient lacking NME3 due to the homozygous mutation at the initiation codon of NME3. Peroxisomes proliferated by elevation of NME3 upon silencing the expression of ATPase family AAA domain containing 1, ATAD1. In the wild-type cells expressing catalytically-inactive NME3, peroxisomes were elongated. These results suggest that NME3 plays an important role in peroxisome division in a manner dependent on its NDP kinase activity. Moreover, the impairment of peroxisome division reduces the level of ether-linked glycerophospholipids, ethanolamine plasmalogens, implying the physiological importance of regulation of peroxisome morphology.

【 授权许可】

Unknown