Rabbit Anti-DNM1L Recombinant Antibody (D1378) (CBMAB-D1378-YC)

dynamin 1-like

DNM1L belongs to the dynamin superfamily of GTPases. DNM1L mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in DNM1L are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF).

Dynamin 1 Like; Dynamin Family Member Proline-Rich Carboxyl-Terminal Domain Less; Dynamin-Related Protein 1; Dnm1p/Vps1p-Like Protein; Dynamin-Like Protein IV; Dynamin-Like Protein 4; EC 3.6.5.5; DYMPLE; HDYNIV;

Functions in mitochondrial and peroxisomal division (PubMed:9570752, PubMed:9786947, PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17553808, PubMed:17460227, PubMed:18695047, PubMed:18838687, PubMed:19638400, PubMed:19411255, PubMed:19342591, PubMed:23921378, PubMed:23283981, PubMed:23530241, PubMed:29478834, PubMed:32484300, PubMed:27145208, PubMed:26992161, PubMed:27301544, PubMed:27328748).

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 (PubMed:23530241, PubMed:23584531).

The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23921378, PubMed:23283981, PubMed:29899447).

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 (PubMed:29899447).

Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300).

Plays an important role in mitochondrial fission during mitosis (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748).

Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (By similarity).

Required for normal brain development, including that of cerebellum (PubMed:17460227, PubMed:27145208, PubMed:26992161, PubMed:27301544, PubMed:27328748).

Facilitates developmentally regulated apoptosis during neural tube formation (By similarity).

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 (By similarity).

Required for formation of endocytic vesicles (PubMed:9570752, PubMed:20688057, PubMed:23792689).

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 (PubMed:17015472, PubMed:23792689).

Required for programmed necrosis execution (PubMed:22265414).

Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834).

Isoform 1&4:
Inhibits peroxisomal division when overexpressed.

Calcium ion transport Source: Ensembl
Cellular response to oxygen-glucose deprivation Source: Ensembl
Cellular response to thapsigargin Source: Ensembl
Dynamin family protein polymerization involved in mitochondrial fission Source: UniProtKB
Heart contraction Source: Ensembl
Intracellular distribution of mitochondria Source: ParkinsonsUK-UCL
Membrane fusion Source: UniProtKB
Mitochondrial fission Source: UniProtKB
Mitochondrial fragmentation involved in apoptotic process Source: UniProtKB
Mitochondrial membrane fission Source: UniProtKB
Mitochondrion morphogenesis Source: MGI
Mitochondrion organization Source: ParkinsonsUK-UCL
Necroptotic process Source: UniProtKB
Negative regulation of mitochondrial fusion Source: Ensembl
Peroxisome fission Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of dendritic spine morphogenesis Source: Ensembl
Positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of mitochondrial fission Source: ParkinsonsUK-UCL
Positive regulation of neutrophil chemotaxis Source: CACAO
Positive regulation of protein secretion Source: UniProtKB
Positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
Positive regulation of synaptic vesicle endocytosis Source: Ensembl
Positive regulation of synaptic vesicle exocytosis Source: Ensembl
Protein complex oligomerization Source: UniProtKB
Protein-containing complex assembly Source: UniProtKB
Protein localization to mitochondrion Source: Ensembl
Regulation of ATP metabolic process Source: Ensembl
Regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
Regulation of gene expression Source: Ensembl
Regulation of mitochondrion organization Source: UniProtKB
Regulation of peroxisome organization Source: UniProtKB
Regulation of ubiquitin protein ligase activity Source: Ensembl
Release of cytochrome c from mitochondria Source: UniProtKB
Response to flavonoid Source: Ensembl
Response to hypobaric hypoxia Source: Ensembl
Rhythmic process Source: UniProtKB-KW
Synaptic vesicle endocytosis Source: Ensembl
Synaptic vesicle recycling via endosome Source: Ensembl

Golgi apparatus; Peroxisome; Mitochondrion outer membrane; Cytosol; Endomembrane system; Clathrin-coated pit; Synaptic vesicle membrane. Mainly cytosolic. Recruited by RALA and RALBP1 to mitochondrion during mitosis (PubMed:21822277). 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 (By similarity). 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 (By similarity).

Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1):
A rare autosomal dominant systemic disorder resulting in lack of neurologic development and death in infancy. After birth, infants present in the first week of life with poor feeding and neurologic impairment, including hypotonia, little spontaneous movement, no tendon reflexes, no response to light stimulation, and poor visual fixation. Other features include mildly elevated plasma concentration of very-long-chain fatty acids, lactic acidosis, microcephaly, deep-set eyes, optic atrophy and hypoplasia, and an abnormal gyral pattern in both frontal lobes associated with dysmyelination.
Optic atrophy 5 (OPA5):
A form of optic atrophy, a disease characterized by progressive visual loss in association with a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA5 is an autosomal dominant non-syndromic form that manifests as slowly progressive visual loss with variable onset from the first to third decades. Additional ocular abnormalities may include central scotoma and dyschromatopsia.

Phosphorylation/dephosphorylation events on two sites near the GED domain regulate mitochondrial fission (PubMed:17301055, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:23283981, PubMed:29478834). Phosphorylation on Ser-637 by CAMK1 and PKA inhibits the GTPase activity, leading to a defect in mitochondrial fission promoting mitochondrial elongation (PubMed:17553808, PubMed:18695047, PubMed:23283981, PubMed:29478834). Dephosphorylated on this site by PPP3CA which promotes mitochondrial fission (PubMed:18838687). Phosphorylation on Ser-616 by CDK1 and PINK1 activates the GTPase activity and promotes mitochondrial fission (PubMed:18838687, PubMed:32484300, PubMed:21822277). Phosphorylated in a circadian manner at Ser-637 (PubMed:29478834).
Sumoylated on various lysine residues within the B domain, probably by MUL1. Sumoylation positively regulates mitochondrial fission. Desumoylated by SENP5 during G2/M transition of mitosis. Appears to be linked to its catalytic activity.
S-nitrosylation increases DNM1L dimerization, mitochondrial fission and causes neuronal damage.
Ubiquitination by MARCHF5 affects mitochondrial morphology.
O-GlcNAcylation augments the level of the GTP-bound active form of DNM1L and induces translocation from the cytoplasm to mitochondria in cardiomyocytes. It also decreases phosphorylation at Ser-637 (By similarity).