Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division
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 rema...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Masanori Honsho Yuichi Abe Yuuta Imoto Zee-Fen Chang Hanna Mandel Tzipora C. Falik-Zaccai Yukio Fujiki |
| author_facet | Masanori Honsho Yuichi Abe Yuuta Imoto Zee-Fen Chang Hanna Mandel Tzipora C. Falik-Zaccai Yukio Fujiki |
| author_sort | Masanori Honsho |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-03-10T15:16:06Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b26987d7d18b4acaae752f67a7ed5d312023-11-20T18:54:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121804010.3390/ijms21218040Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome DivisionMasanori Honsho0Yuichi Abe1Yuuta Imoto2Zee-Fen Chang3Hanna Mandel4Tzipora C. Falik-Zaccai5Yukio Fujiki6Medical Institute of Bioregulation, Institute of Rheological Functions of Food—Kyushu University Collaboration Program, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, JapanMedical Institute of Bioregulation, Institute of Rheological Functions of Food—Kyushu University Collaboration Program, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, JapanDepartment of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USAInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, TaiwanGalilee Medical Center, Institute of Human Genetics, Nahariya 22100, IsraelGalilee Medical Center, Institute of Human Genetics, Nahariya 22100, IsraelMedical Institute of Bioregulation, Institute of Rheological Functions of Food—Kyushu University Collaboration Program, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, JapanPeroxisomes 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.https://www.mdpi.com/1422-0067/21/21/8040peroxisomeconstrictionNDP kinaseGTP<i>nme3</i> patient |
| spellingShingle | Masanori Honsho Yuichi Abe Yuuta Imoto Zee-Fen Chang Hanna Mandel Tzipora C. Falik-Zaccai Yukio Fujiki Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division International Journal of Molecular Sciences peroxisome constriction NDP kinase GTP <i>nme3</i> patient |
| title | Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division |
| title_full | Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division |
| title_fullStr | Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division |
| title_full_unstemmed | Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division |
| title_short | Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division |
| title_sort | mammalian homologue nme3 of dynamo1 regulates peroxisome division |
| topic | peroxisome constriction NDP kinase GTP <i>nme3</i> patient |
| url | https://www.mdpi.com/1422-0067/21/21/8040 |
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