DNM1L
GeneName
DNM1L
Summary
DNM1L, also known as DRP1 or dynamin related protein 1, is an 82 kDa GTPase that plays a pivotal role in mitochondrial dynamics, particularly in mitochondrial fission. It is localised to various cellular compartments including the mitochondrial outer membrane, endoplasmic reticulum, Golgi apparatus, and cytoplasm. DNM1L is involved in processes such as endocytosis, calcium ion transport, and the intracellular distribution of mitochondria, and it facilitates the fragmentation of mitochondria, which is crucial for apoptosis and cellular homeostasis. The protein functions through GTP binding and hydrolysis, enabling it to interact with lipid membranes and other proteins, thereby regulating mitochondrial morphology and function.
Importance
DNM1L is relevant to: - Mitochondrial dynamics and cellular energy metabolism, as it regulates mitochondrial fission and fusion processes - Neurodegenerative diseases, where mitochondrial dysfunction is a key feature - Apoptosis and cell death mechanisms, given its role in mitochondrial fragmentation during these processes - Inflammatory responses, due to its involvement in neutrophil chemotaxis and protein secretion regulation
Top Products
For researchers investigating DNM1L, we recommend two excellent primary antibodies. The first is the well-cited Anti-DRP1 antibody [3B5] (ab56788), which has garnered 229 citations and is particularly effective for immunohistochemistry (IHC), immunoprecipitation (IP), and flow cytometry (FC). This antibody is a trusted choice for many in the field. Additionally, we offer the recombinant antibody, Anti-DRP1 antibody [EPR19274] (ab184247), which has an impressive 257 citations. This versatile product is validated for a broad range of applications, including Western blotting (WB), immunocytochemistry (ICC), IHC, IP, and FC. The recombinant nature of this antibody ensures batch-to-batch consistency, making it an ideal option for researchers seeking reliable detection of DNM1L. The Recombinant Human DRP1 protein ELISA Kit (ab153041), supported by 1 citation, is a reliable option for researchers looking to measure DNM1L in their experiments.
Abcam Product Citation Summary
The data indicates a strong focus on the role of DNM1L in mitochondrial dynamics across various species, including humans and rodents. Studies often involve conditions such as diabetic retinopathy, traumatic brain injury, and ischemia-reperfusion, highlighting the importance of DNM1L in cellular responses to stress and injury. The use of both Western blotting and immunohistochemistry suggests a comprehensive approach to understanding DNM1L's function in different biological contexts.
Abcam Product Citation Table
Domain
The GED domain folds back to interact, in cis, with the GTP-binding domain and middle domain, and interacts, in trans, with the GED domains of other DNM1L molecules, and is thus critical for activating GTPase activity and for DNM1L dimerization.
Function
Functions in mitochondrial and peroxisomal division (PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17460227, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:19342591, PubMed:19411255, PubMed:19638400, PubMed:23283981, PubMed:23530241, PubMed:23921378, PubMed:26992161, PubMed:27145208, PubMed:27145933, PubMed:27301544, PubMed:27328748, PubMed:29478834, PubMed:32439975, PubMed:32484300, PubMed:9570752, PubMed:9786947). 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, PubMed:33850055). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, PubMed:23921378, 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:26992161, PubMed:27145208, 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:20688057, PubMed:23792689, PubMed:9570752). 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
Inhibits peroxisomal division when overexpressed.
Isoform 4
Inhibits peroxisomal division when overexpressed.
Involvement in disease
May be associated with Alzheimer disease through amyloid-beta-induced increased S-nitrosylation of DNM1L, which triggers, directly or indirectly, excessive mitochondrial fission, synaptic loss and neuronal damage.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
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, PubMed:33850055). 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:21822277, PubMed:32484300). Phosphorylated in a circadian manner at Ser-637 (PubMed:29478834). Dephosphorylated by PGAM5 (PubMed:32439975).
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).
Sequence Similarities
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
Tissue Specificity
Ubiquitously expressed with highest levels found in skeletal muscles, heart, kidney and brain. Isoform 1 is brain-specific. Isoform 2 and isoform 3 are predominantly expressed in testis and skeletal muscles respectively. Isoform 4 is weakly expressed in brain, heart and kidney. Isoform 5 is dominantly expressed in liver, heart and kidney. Isoform 6 is expressed in neurons.
Cellular localization
- Cytoplasm
- Cytosol
- Golgi apparatus
- Endomembrane system
- Peripheral membrane protein
- Mitochondrion outer membrane
- Peripheral membrane protein
- Peroxisome
- Membrane
- Clathrin-coated pit
- Cytoplasmic vesicle
- Secretory vesicle
- 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 (PubMed:17606867). Localizes to mitochondria at sites of division (PubMed:15208300). 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 (PubMed:9422767, PubMed:9570752). In some cell types, localizes to the Golgi complex (By similarity). Binds to phospholipid membranes (By similarity).
Alternative names
DLP1, DRP1, DNM1L, Dynamin-1-like protein, Dnm1p/Vps1p-like protein, Dynamin family member proline-rich carboxyl-terminal domain less, Dynamin-like protein, Dynamin-like protein 4, Dynamin-like protein IV, Dynamin-related protein 1, DVLP, Dymple, HdynIV