Literature summary for 3.6.5.5 extracted from

Ji, W.K.; Hatch, A.L.; Merrill, R.A.; Strack, S.; Higgs, H.N.
Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites (2015), eLife, 4, e11553 .

Search for more literature for 3.6.5.5

Activating Compound

Activating Compound	Comment	Organism	Structure
actin	actin filaments bind purified Drp1 and increase GTPase activity in a manner that is synergistic with the mitochondrial protein Mff, suggesting a role for direct Drp1/actin interaction	Homo sapiens
actin	actin filaments increase Drp1's GTPase activity eith a 3.5fold increase. The assembly of filaments of actin is the signal to Drp1 to accumulate on mitochondria and for fission	Homo sapiens
cardiolipin	Drp1 binding to anionic lipids such as cardiolipin increases its GTPase activity	Homo sapiens
ionomycin	a calcium ionophore, causes rapid mitochondrial accumulation of actin filaments followed by Drp1 accumulation at the fission site, and increases fission rate	Homo sapiens
Mff protein	mitocjondrial protein Mff alone causes only a slight increase in Drp1 GTPase activity at the concentrations tested, while the combination of Mff and actin filaments causes a substantial increase in Drp1 activity, far beyond the additive effects of either Mff or actin alone	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of N-terminally Strep-tagged Drp1 with an HRV3C protease site from pET16b vector in Escherichia coli strain BL21 Star (DE3), stable recombinant expression of GFP-tagged DrpI in U2OS cells with partial shRNA suppression of endogenous Drp1 (gDrp-U2OS), GFP-Drp1 functionally compensates for endogenous Drp1 in these cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	partial shRNA suppression of endogenous Drp1 (gDrp-U2OS). GFP-Drp1 functionally compensates for endogenous Drp1 in these cells. gDrp-U2OS cells maintain 1.64fold total Drp1 levels compared to control U2OS cells, with 56% endogenous Drp1 and 44% GFP-Drp1. The fission rates of control U2OS and gDrp1-U2OS cells are statistically similar. A second clone displaying undetectable endogenous Drp1 levels and GFP-Drp1 levels about 3.5fold higher than control Drp1 levels shows similar mitochondrial fission frequency compared to control cells. By live-cell confocal microscopy, much of the GFP-Drp1 in gDrp-U2OS cells appears diffuse in the cytoplasm	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	Drp1 is a cytosolic protein that translocates to the outer mitochondrial membrane	Homo sapiens	5829	-
mitochondrial outer membrane	Drp1 is a cytosolic protein that translocates to the outer mitochondrial membrane	Homo sapiens	5741	-
additional information	actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites. Cytosolic Drp1 is recruited directly to fission sites immediately prior to fission. Progressive maturation of Drp1 oligomers on mitochondria through incorporation of smaller mitochondrially-bound Drp1 units. Maturation of a stable Drp1 oligomer does not forcibly lead to fission. Drp1 oligomers also translocate directionally along mitochondria. Drp1 is a cytosolic protein that translocates to the outer mitochondrial membrane	Homo sapiens	-	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
GTP + H2O	Homo sapiens	-	GDP + phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O00429	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
additional information	actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites	Homo sapiens

Purification (Commentary)

Purification (Comment)	Organism
recombinant N-terminally Strep-tagged Drp1 from Escherichia coli strain BL21 Star (DE3) by affinity chromatography, followed by tag cleavage by HRV3C protease, and gel filtration	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
U2-OS cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
GTP + H2O	-	Homo sapiens	GDP + phosphate	-	?

Subunits

Subunits	Comment	Organism
oligomer	in solution, Drp1 exists in a number of oligomeric states, including dimers, tetramers, and higher-order oligomers. Actin filaments can organize Drp1 into a productive oligomer	Homo sapiens

Synonyms

Synonyms	Comment	Organism
Drp1	-	Homo sapiens
dynamin GTPase	-	Homo sapiens
dynamin-1	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
23	-	GTPase and polymerization assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	GTPase and polymerization assay at	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	suppression of either INF2 or myosin IIA causes an 50% decrease in fission rate, whereas Drp1 suppression or expression of the dominant-negative Drp1 K38A mutant cause near-complete inhibition. In addition, suppression of either INF2 or myosin IIA reduces mitochondrially-associated Drp1 puncta, with a moderate reduction of total Drp1 puncta (2.7fold for both INF2 and myosin IIA) and a larger reduction in high threshold puncta (6.7fold and 8.3fold, respectively). LatA treatment also causes a reduction in mitochondrially-associated Drp1 puncta, although the degree of high threshold reduction is not as great as for INF2 or myosin IIA suppression	Homo sapiens
physiological function	the large GTPase dynamin mediates membrane fission during clathrin-mediated endocytosis (CME). Dynamin GTPase Drp1 plays a critical role during mitochondrial fission, cytosolic Drp1 is recruited directly to fission sites immediately prior to fission. Progressive maturation of Drp1 oligomers on mitochondria through incorporation of smaller mitochondrially-bound Drp1 units. Maturation of a stable Drp1 oligomer does not forcibly lead to fission. Drp1 oligomers also translocate directionally along mitochondria. Drp1 is in dynamic equilibrium on mitochondria in a fission-independent manner, and fission factors such as actin filaments target productive oligomerization to fission sites. The assembly of filaments of actin is the signal to Drp1 for fission. Differential affinities of Drp1 oligomeric states for actin filaments	Homo sapiens

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Release 2023.1 (January 2023)