Onsite GTP fuelling via DYNAMO1 drives division of mitochondria and peroxisomes

Yuuta Imoto,Yuichi Abe,Masanori Honsho,Tsuneyoshi Kuroiwa,Haruko Kuroiwa,Kanji Okumoto,Yukio Fujiki,Mio Ohnuma

doi:10.1038/s41467-018-07009-z

Abstract

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.

Highlights

When the histidine residue at position 116 of dynamin-based ring motive-force organizer 1 (DYNAMO1) in the consensus active site motif was replaced by aspartic acid (DYNAMO1 H116D), its GTP generation was abolished (Fig. 1e), demonstrating that DYNAMO1 functions as a nucleoside diphosphate kinase
Because nucleoside diphosphate kinase is involved in dynamin-mediated endocytosis and OPA1-mediated mitochondrial fusion in mammalian cells[29,30], we suggest that DYNAMO1 is involved in Dnm1-based organelle division machineries
Here, we demonstrated that a novel component, DYNAMO1, of mitochondrial division (MD) and POD machineries is an essential molecule for the division of both mitochondria and peroxisomes

Summary

Introduction

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 Dnm[1] that requires a large amount of GTP as an energy source. Accessory proteins of Dnm[1], such as Fis[1], Mdv[1], Mff, and MiDs, might enhance the kinetics of its GTP affinity and facilitate membrane constriction[11] Conservation of these proteins among eukaryotes is limited, even though Dnm1-mediated division of mitochondria and peroxisomes is common to almost all eukaryotic cells including those in animals, fungi, land plants, and algae[12]. Energy source for the constriction of MD and POD machineries is most likely generated locally around the membrane scission sites during the division of mitochondrion and peroxisome

Methods

Results

Conclusion