Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division

• Main Authors: Masanori Honsho, Yuichi Abe, Yuuta Imoto, Zee-Fen Chang, Hanna Mandel, Tzipora C. Falik-Zaccai, Yukio Fujiki
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: peroxisome; constriction; NDP kinase; GTP; <i>nme3</i> patient
• Online Access: https://www.mdpi.com/1422-0067/21/21/8040
• ISSN: 1661-6596; 1422-0067

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, <i>Cyanidioschyzon merolae.</i> 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 <i>NME3 </i>and fibroblasts from a patient lacking NME3 due to the homozygous mutation at the initiation codon of <i>NME3</i>. Peroxisomes proliferated by elevation of NME3 upon silencing the expression of ATPase family AAA domain containing 1, <i>ATAD1</i>. 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.