Protein: Dynamin-1-like protein (EC 3.6.5.5) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-related protein 1) (Q8K1M6)
Organism: Mus musculus (Mouse)
Function: Functions in mitochondrial and peroxisomal division. Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism. The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes. While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane. Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner. Plays an important role in mitochondrial fission during mitosis (By similarity). Required for formation of endocytic vesicles (By similarity). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage. Required for normal brain development, including that of cerebellum. Facilitates developmentally regulated apoptosis during neural tube formation. Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues. Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles (By similarity). Required for programmed necrosis execution (By similarity). Rhythmic control of its activity following phosphorylation at Ser-643 is essential for the circadian control of mitochondrial ATP production.
Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:30059978}. Golgi apparatus {ECO:0000250|UniProtKB:O00429}. Endomembrane system {ECO:0000250|UniProtKB:O00429}. Mitochondrion outer membrane {ECO:0000269|PubMed:30059978, ECO:0000305|PubMed:29853636}; Peripheral membrane protein. Peroxisome {ECO:0000269|PubMed:29853636}. Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:O35303}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:O35303}. Note=Mainly cytosolic. Recruited by RALA and RALBP1 to mitochondrion during mitosis (By similarity). Translocated to the mitochondrial membrane through O-GlcNAcylation and interaction with FIS1. Colocalized with MARCHF5 at mitochondrial membrane. Localizes to mitochondria at sites of division. Localizes to mitochondria following necrosis induction. Recruited to the mitochondrial outer membrane by interaction with MIEF1. Mitochondrial recruitment is inhibited by C11orf65/MFI (PubMed:30059978). Associated with peroxisomal membranes, partly recruited there by PEX11B. May also be associated with endoplasmic reticulum tubules and cytoplasmic vesicles and found to be perinuclear. In some cell types, localizes to the Golgi complex (By similarity). Binds to phospholipid membranes. {ECO:0000250, ECO:0000250|UniProtKB:O00429, ECO:0000269|PubMed:30059978}.; SUBCELLULAR LOCATION: [Isoform 14]: Lysosome {ECO:0000269|PubMed:29853636}. Late endosome {ECO:0000269|PubMed:29853636}. Cell membrane {ECO:0000269|PubMed:29853636}; Peripheral membrane protein. Mitochondrion outer membrane {ECO:0000269|PubMed:29853636}; Peripheral membrane protein. Postsynaptic density {ECO:0000269|PubMed:31603426}. Note=Is recruited to existing interorganelle interfaces between mitochondria and lysosomes/ late endosomes (PubMed:29853636). GTP hydrolysis and oligomerization are required for its localization to lysosomes/late endosomes and the cell membrane (PubMed:29853636). {ECO:0000269|PubMed:29853636}.
Interaction partners:
- Mitochondrial dynamics protein MID51
- Mitochondrial fission factor
- Mitochondrial dynamics protein MID49
- Mitochondrial fission 1 protein
- Serine/threonine-protein phosphatase PGAM5, mitochondrial
- Mitofusin-2
- Receptor-interacting serine/threonine-protein kinase 3
- Receptor-interacting serine/threonine-protein kinase 1
- Mitofusin-1
- FUN14 domain-containing protein 1
Sequence:
MEALIPVINKLQDVFNTVGADIIQLPQIVVVGTQSSGKSSVLESLVGRDLLPRGTGVVTRRPLILQLVHVSPEDKRKTTGEENGVEAEEWGKFLHTKNKLYTDFDEIRQEIENETERISGNNKGVSPEPIHLKVFSPNVVNLTLVDLPGMTKVPVGDQPKDIELQIRELILRFISNPNSIILAVTAANTDMATSEALKISREVDPDGRRTLAVITKLDLMDAGTDAMDVLMGRVIPVKLGIIGVVNRSQLDINNKKSVTDSIRDEYAFLQKKYPSLANRNGTKYLARTLNRLLMHHIRDCLPELKTRINVLAAQYQSLLNSYGEPVDDKSATLLQLITKFATEYCNTIEGTAKYIETSELCGGARICYIFHETFGRTLESVDPLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKRLEEPSLRCVELVHEEMQRIIQHCSNYSTQELLRFPKLHDAIVEVVTCLLRKRLPVTNEMVHNLVAIELAYINTKHPDFADACGLMNNNIEEQRRNRLARELPSAGSRDKSSKVPSALAPASQEPPPAASAEADGKLIQDNRRETKNVPSAGGGIGDGGQEPTTGNWRGMLKTSKAEELLAEEKSKPIPIMPASPQKGHAVNLLDVPVPVARKLSAREQRDCEVIERLIKSYFLIVRKNIQDSVPKAVMHFLVNHVKDTLQSELVGQLYKSSLLDDLLTESEDMAQRRKEAADMLKALQGASQIIAEIRETHLW