naL ac,PnrS ue n er .Higgs* N. Henry and Gurel S. Pinar fission Hatch, L. mitochondrial Anna in actin for roles Novel COMMENTARY ß Ato o orsodne([email protected]) correspondence for *Author Hanover, Dartmouth, at Medicine USA. of 03755, School NH Geisel Biochemistry, of Department the of function major A NAD of host. amounts large original and production, the ATP is from mitochondrion and came (Mileykovskaya (OMM) membrane likely endosymbiont mitochondrial outer bacterial the 1898). whereas 2009), the Dowhan, (Benda, of (IMM) remnants ‘mitos’, granule membrane are mitochondrial terms mitochondrial inner for Greek cardiolipin-rich the and relationship, the genome ‘chondros’ endosymbiotic of an from and combination Originating renamed a thread, were as mitochondria meaning later 1890, in years bioblasts eight as described First Introduction Myosin fission, Mitochondrial Actin, multiple WORDS: that KEY possibility mammals. the in discuss exist we mechanisms for fission addition, detector In coincidence a binding. as pre- and Drp1 for serving force actin by the secondly, which supplying and by in constriction firstly, ways; fission two in mitochondrial contribute for myosin actin- present model other we Commentary, and mechanistic this II In a myosin involved. be that might and proteins ER-associated Drp1, binding of the upstream requires INF2 that formin mammals an be in force might Drp1 process ERMD to actin-based that the leads show however, pre-constriction generates results, Recent why recruitment. contact or pre-constriction ER–mitochondrial for the required how It which division). unclear mitochondrial in (ER-associated is step ERMD termed pre-constriction process extensively, interact a a mitochondrion and (ER) require reticulum endoplasmic to event, regulatory appears key a and which is (OMM) to site membrane recruitment mitochondrial fission Drp1 outer ingression. the the dynamin- membrane at drive cytoplasmic to oligomerizes the GTP which hydrolyzes is Drp1, fission GTPase in neurodegenerative related player several central with A links polarity, diseases. received to cellular has owing in fission attention, Mitochondrial roles particular apoptosis. with and homeostasis, response cellular stress to translocation, crucial and are fission fusion, including dynamics, Mitochondrial ABSTRACT iso LwsadLws 94.Hwvr oimmediate past no the Within However, dynamics. these 1914). to Lewis, attributed was and undergoing significance and (Lewis fusing moving, fission constantly – of dynamic mitochondrial incredibly question the the raising mitigated. is 2012), mechanisms, of damage Bliek, DNA repair der mitochondrial susceptibility how van DNA and mutational (Youle limited genome the with coupled this increases In process, radicals. matrix. free creating mitochondrial lost, This become can the some electrons, in of flux cycles large redox undergo FADH 04 ulse yTeCmayo ilgssLd|Junlo elSine(04 2,44–50doi:10.1242/jcs.153791 4549–4560 127, (2014) Science Cell of Journal | Ltd Biologists of Company The by Published 2014. n11,LwsadLwsntdta iohnrawere mitochondria that noted Lewis and Lewis 1914, In + and hro-ai-ot ies.Anme fecletrecent excellent of and number diseases, ALS A neurodegenerative Parkinson’s, disease. many Huntington’s, Charcot-Marie-Tooth of Alzheimer’s, pathogenesis including the polarized associated highly intimately with are the dynamics to mitochondrial neurons, Owing of polarization. state cell and mitochondrial division during addition, distribution cell mitochondrial In proper role. for required a are fission play dynamics the to which appears in apoptosis, also remove (3) machinery or to product; mitophagy fission subsequent damaged with the segment, healthy of segment damaged the segregation the from of (2) fission a damage; by followed with the components damaged fusion spread possible (1) to several oxidative mitochondrion damage: are healthy oxidative from there mitochondrial clear that protection the to is responses to in emerging owing picture dynamics interest, The mitochondrial damage. renewed a of been role has there years, 20 ekn n limn 01 aa n ota 02.In 2012). multiple fission. 2008; be Mootha, in al., might participates and actin there et which that Noske Vafai by possibility 2012; mechanisms the al., 2011; al., present et we et Ellisman, Hu addition, Kim 1984; be and 2013; al., can al., et Perkins force et (Goldstein which myosin Jans in only and 2013; of ways actin range possible by the the applied in restrict frequently nm, diameters 150–300 with types, from mitochondria cell mammalian of many mechanisms. widths narrow possible the the instance, of on For constraints sizes mitochondrion put relevant ER, a apparatus the constrictive the fission of highlight dimensions and produce construct to the because is might players, model we key our the actin of and goal how One force. for fission, model mitochondrial mechanistic in cytoskeleton van and Youle 2012). 2012; Bliek, Mootha, der and Vafai 2012; Suomalainen, Nunnari 2012; 2012; and Nunnari, Chan, and 2013; Hoppins 2014; (Archer, Nunnari, detail and Friedman in subjects these cover reviews t osrcinatvt per ob rvn oc nfission in force driving a be to 1A). and appears (Fig. causes sites, activity fission hydrolysis mitochondrial constriction at its GTP accumulates Drp1 2014). 2011). lipid Mears al., 2013; al., al., et anionic et (Koirala et membrane tubulate tubulated the Macdonald of to constriction 2013; ability al., the et has it (Fro membranes and number a conditions, under oligomers of higher-order 2001; into assembles that al., dimer domain (Fro GTPase et end the structure with one crystal elongated, Boldogh is The at it 1998). that 1999; al., shows and Drp1 et human al., Otsuga of yeast 1999; et al., in et (Bleazard Labrousse work Dnm1, factor with as fission Dymple), and to elegans Caenorhabditis Dnm1l referred Dvlp1, (also GTPase Dlp1, dynamin-related eukaryotes a throughout is in conserved Drp1 protein central Drp1. a describe fission, we mitochondrial actin, of questions role the outstanding discussing and Before factors – fission Mitochondrial hsCmetr oue ntepriiaino h actin the of participation the on focuses Commentary This hihe l,21) uiidDp sa X-shaped an is Drp1 Purified 2013). al., et ¨hlich hihe l,21;Igra ta. 05 Koirala 2005; al., et Ingerman 2013; al., et ¨hlich rgnlyietfigi samitochondrial a as it identifying originally 4549

Journal of Cell Science COMMENTARY 4550 have Caf4 or Mdv1 MiD49 to Mff, mammals. homologous Fis1, in are – identified that OMM receptors been proteins possible Drp1 adaptor four as No mammals, act MiD51. In to and adaptor Mdv1. postulated second of been Dnm1 A place have the oval). in proteins to the act binds by can turn represented Caf4, in Fis1 is protein, which protein domain Mdv1, OMM GTPase protein the (its adaptor yeast, dimer budding dimeric In the budding (right). to in mammals binds receptors in fission Dnm1/Drp1 and 4: (B) (left) Step mechanism. yeast the site. unknown by fission an hydrolysis the by GTP of occurs 3: constriction Step causes binds oligomerizes. Drp1 Drp1 and oligomerized 2: site Step (orange). pre-constriction ‘pre- Drp1 the is of undergoes to arrival site site the fission to this prior a and (asterisk) 1: mechanism, constriction’ Step unknown fission. an mitochondrial by in marked fission. involved mitochondrial steps in general Drp1 the of Role 1. Fig. h iohnro nclsta r opoie o Drp1 for compromised ‘pre- Drp1-independent are a been that that hypothesis has the It cells to along recruited? leading points in activity, Drp1 specific at mitochondrion is occurs still how the constriction and some that site shown fission a defines tr ta. 00 amre l,21)(i.1) eo,we represent Below, receptors 1B). multiple (Fig. fission. these 2011) mitochondrial of al., that variations et mechanistic possibility Palmer the 2010; 2008; discuss al., Bliek, der et van – and Otera receptors (Gandre-Babbe Drp1 MiD51 single-pass and potential other MiD49 as Three Mff, identified mitophagy 2014). been during al., have et Fis1 proteins Yamano OMM for 2014; exciting role al., However, a et 2013). (Shen demonstrated al., has et Palmer Loso work 2013; 2010; recent (Gandre- al., al., et studies et Koirala between Otera 2008; 2013; variable Bliek, der been van have and effects Babbe fission the on and homologs, Fis1 recruits adaptor of then metazoans obvious Although which lack clear. 2005; they of less Fis1, either al., is possess 2002), picture et the al., mammals, (Griffin et In two well Tieu 1B) Dnm1. of 2012; (Fig. relatively one al., Caf4 et to is or Guo binds recruitment Mdv1 Fis1 proteins, Dnm1 protein adaptor OMM yeast, single-pass In the defined: OMM? the on raises then recruitment? pre- does Drp1 model How trigger occur? this constriction pre-constriction 1999; However, does al., How et 2003). questions. Labrousse other 1A) al., 2004; (Fig. al., et et recruitment Koch Legesse-Miller Drp1 2011; al., for et necessary (Friedman is event constriction’ A B Mitochondrion utemr,wa r h r1‘eetr’ta idt Drp1 to bind that ‘receptors’ Drp1 the are what Furthermore, what initiated, fission is how are: field the in questions Major OMM Dnm1 Mdv1 Fis1 Pre-constriction Yeast Mammals 1 2 C N * oligomerization Fis1 Mff Mff Fis1 Drp1 binding N C and Fission A ceai lutainof illustration Schematic (A) 4 N Mid49/51 C N GTP and constriction GTP hydrolysis GDP +Pi ´ tal., et n 3 iohnra iso rwa ol sebeteeactin these influence assemble could would actin what how clear or not fission was actin mitochondrial it of Drp1 However, distribution in 2012). and or length levels mitochondrial in the it recruitment in Subsequently, in alterations 2005). cause changes al., filaments that et Vos shown (De CV1- was in cells poisons kidney mitochondrial monkey several actin-depolymerizing 4A by mitochondrial mediated that in is reduction that observation the length and recruitment mitochondrial the Drp1 in inhibit role from drugs a play came might fission actin fission mitochondrial that in suggestion myosin first and The INF2 actin, for Evidence eessteefc fcntttvl cieIF (short INF2 active also inhibition constitutively II of Myosin 2012). effect al., the et 2014) (DuBoff al., reverses et ML-7 (Korobova blebbistatin and cause mitochondrial – also bound inhibitors causes elongation mitochondrially molecule mitochondrial 2014) small of myosin-directed amount al., Two chains the Drp1. heavy et IIB decreases or (Korobova and IIA elongation cells myosin Cos7 of in U2OS or (MRLC) 2012) 2B). in al., chain (Fig. et 2013) light (DuBoff al., regulatory cells et myosin (Billington motor- of end 14–30 Suppression each II contain at myosin that heads the filaments non-muscle containing being IIB anti-parallel mammalian and form All IIA paralogs with expressed. IIC, non-muscle widely and IIB mammalian most IIA, three paralogs, II are myosin There fission. mitochondrial depletion active constitutively INF2 2013). al., by Drp1; et (Korobova fragmentation of INF2 inhibition mitochondrial upstream Drp1 and reduces acts evidence Drp1, Karbowski, mitochondrially-associated of INF2 M. decreases lines Actin in that 2013; two that al., suggest results 2013). Furthermore, sites et communication). INF2-ER contact al., (Korobova personal ER–mitochondrial of constriction et at undergo that (Korobova accumulate 2011), filaments elongation al., fragmentation mitochondrial Golgi et causes 2011). INF2-Cyto (Ramabhadran al., of et Ramabhadran suppression 2009; Whereas al., et INF2-Cyto (Chhabra two and cytosolic ER-bound being creates being INF2-ER nine- essentially with proteins, non-prenylated difference different This a C-terminus. contains amino-acid INF2-nonCAAX) variant called INF2-Cyto the (also that whereas C-terminus prenylated, 18-amino-acid post-translationally two (also is an additional variant as contains INF2-ER expressed has The INF2-CAAX) is C-termini. INF2 INF2 called their 1). at 2005). differ Box that (see (Higgs, isoforms filaments 2A) actin (Fig. end actin on ‘barbed’ effects of filament fast-growing elongation the the and to of binding nucleation their the through both filaments factors accelerate actin-assembly are can Formins that 2013). al., et (Korobova INF2 filaments. r-osrcin nldn usin bu h mechanism the about pre-constriction. for force questions the providing mediates al., ER including the et unknown. how is (Friedman regarding pre-constriction, enrichment questions has points its many are to Mff, contact there leading receptor, Overall, at mechanism Drp1 enriched the but one be 2011), least to At shown constrict. and been mitochondria still around sites wraps still these ER in the Interestingly, called cells, process Drp1-deficient division). a mitochondrial in – wrapped (ER-associated 2011) is ERMD al., ER et at the (Friedman occurs where mitochondria often areas around fission – showed sites that contact study mitochondrial–ER elegant an in addressed onigeiec ugssta ysnI loat in acts also II myosin that suggests evidence Mounting formin the through ERMD to actin linked study recent more A h usino htatvtsDp erimn a been has recruitment Drp1 activates what of question The ora fCl cec 21)17 5946 doi:10.1242/jcs.153791 4549–4560 127, (2014) Science Cell of Journal Drosophila ern n o- el DBf tal., et (DuBoff cells Cos-1 and neurons

Journal of Cell Science COMMENTARY nulse bevtos.Teaiiyt idt ci filaments actin to H.N.H., bind and to (A.L.H. ability affinity, Drp1 The sub-micromolar of observations). rate Using with unpublished hydrolysis 2012). filaments GTP the actin al., Drp1 increasing mammalian to et that to binds evidence (DuBoff found appears directly actin have we II and co- proteins, Myosin the purified Drp1 reduce 2012). of mutants myosin al., precipitation because interaction, et this (DuBoff the enhance filaments between actin In relationship filaments. actin reciprocal myosin. al., and et a actin (DuBoff from of flies accumulation suggesting mutant Results myosin in 2012), filaments. reduced INF2- is actin requires mitochondria recruitment of II Drosophila polymerization myosin that al., mediated et (Korobova suggesting manner INF2-dependent 2014), to an localizes in MRLC sites Active constriction 2014). al., et (Korobova t are mitochondria) filament the of m ends anti-parallel barbed on the here, filament shown II example myosin The the bipolar end. In formin. the membrane. barbed a of the the activity by of to Motor constriction membrane addition deformation. thus monomer the and membrane directing to structure, deformation com Myosin-II-based of membrane the size (D) compact the example causes for blue. to ‘10S’ classic filaments shown in tethered actin a the also shown formin attached Left, assumes is are a ends. diameter of II formin example barbed mitochondrial and myosin prese ATP, an ‘typical’ complex filament the Right, A of 3 membrane-abutting in shown. b cells. presence to structure is non-muscle a compact the addition nucleation in create the monomer In dendritic documented from to complex-based by center. been assembly further deformation not the filament oligomerize has membrane bipolar in can and for Actin-polymerization-based zone’ observation II allows (C) ‘bare biochemical phosphorylation myosin a a RLC non-muscle segments. is and panel, chai three latter end light Lower into The each essential tail structure. of two the at the tails chains, folding heads dominate coiled-coil by heavy their domain chains presumably two by motor heavy of parallel the dimerized complex in multi-protein the with dimerized a tightly because filament is are ‘dimer’ II chains f the s heavy myosin biochemistry, sever as The releas of INF2 to phosphate (RLC). unit unit regarding and chains able fundamental details hydrolysis light additionally the further ATP regulatory For panel, is Upon controllin two depolymerization. them. Upper INF2 by and enhances encircling II. panel, rate subsequently by myosin Lower and filaments elongation Non-muscle filament 2010. of (B) regulating the sides al., 2014. severs the filament, et INF2 to elongating Chesarone filament, bind the the and to in ability of 2005 subunits its Higgs, end through see barbed depolymerization biochemistry, their the formin enhance at and regarding remains detail it more Subsequently, For (red). addition. monomers constriction. actin membrane of actin-based nucleation of Mechanisms 2. Fig. ial,teei nraigeiec htDp neat with interacts Drp1 that evidence increasing is there Finally, C A Force Barbed hwta h muto ci soitdwith associated actin of amount the that show Severing actin polymerization Pointed Arp2/3-mediated Formin-mediated nucleationandelongation Drosophila INF2 severinganddepolymerization + xrcs r1c-rcpttswith co-precipitates Drp1 extracts, Key actin polymerization Barbed Formin-mediated Depolymerization Formin Pointed Barbed Membrane Pointed A h fet ffriso ci.Uprpnl omndmr(le a nac the enhance can (blue) dimer formin a panel, Upper actin. on formins of effects The (A) Myosin IIfilament r loal obn oatnflmns(ue l,2010). al., et (Gu filaments actin and to 1 bind dynamin to both able as also family, are dynamin 2 the to common be might oiiy hra ysnI-ae ocspwrsrs fiber stress cell power during forces protrusion myosin-II-based edge leading thereby whereas II and myosin motility, membrane, bipolar endocytosis of are attached actin-polymerization-induced case force of the Examples and 2C,D). in motors (Fig. myosin force filaments filament polymerization that constrictive (2) a actin actin or producing it, the that of front ‘pull’ (1) in general membrane two proposed: the with years, ‘pushes’ many being for research mechanisms intense been of has membranes subject be on the force generation this force might fission Actin-based How the generated? pre-constriction. at driving Drp1 by II of perhaps myosin accumulation site, and the actin facilitate to INF2, together that work imply above discussed results The fission mitochondrial actomyosin-mediated for model Mechanistic D B Membrane ora fCl cec 21)17 5946 doi:10.1242/jcs.153791 4549–4560 127, (2014) Science Cell of Journal Mitochondrion 240 nm Compact Dimer Barbed Actin filament Force , 6 mlnt.W ee oti fundamental this to refer We length. nm 160 Motor movement 300 nm 160 nm 167 nm Filament Barbed eGrle al., et Gurel ee monomer g rmactin from e c fATP. of nce embrane- s(ELC) ns ilaments parison. ethered Arp2/3- 4551 ipolar Arp2/

Journal of Cell Science COMMENTARY 4552 2012). al., et (Proctor septation as by the such driven forces, be in other to by appear early but not ring. myosin, required does ring is full ingression cytokinetic the activity membrane of constriction motor process, plasma compact myosin in Although more results 3). (Fig. ring the this of myosin-II- into Constriction their in focusing results Formin-mediated nodes mediated these ‘nodes’. from called polymerization structures, actin molecular precursor cleavage 2012; prospective of in the al., at et furrow set accumulates (Lee II clear defined Myosin been a 2010). has Pollard, events which of for sequence and for yeast, factors model fission best-studied is The cytokinesis division. and constriction of membrane flow 2014). retrograde al., the et and (Blanchoin networks contraction actin cortex cell contraction, ihms omn,IF ceeae h ulaino e actin new of nucleation the accelerates INF2 filaments As formins, in factors. assembly (15 most filament proteins actin with actin-binding as act are generally Formins that protein. mammals) formin a INF2 is of INF2 properties biochemical The 1. 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Fig. ufc,adta atrlclzda h M csa nINF2 ER receptors. an the Drp1 as the acts of at OMM one be or the even at might cytoplasm localized molecule This the factor activator. interaction a in that the DID–DAD either and on surface, additional exist, the that state propose factors requires therefore ‘off’ inhibitory We 2013). an inhibition al., in et and interaction (Ramabhadran clearly this al., ER, is et and bulk INF2 (Ramabhadran monomers, interaction Nevertheless, the actin DID–DAD 2013). 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Journal of Cell Science COMMENTARY sta h iaetbre n ean ehrdt h ER the to tethered remains end barbed filament the result nucleation the nucleator, that filament the Whatever is proteins. actin other or in site INF2 fission through results the at contact production filament ER–mitochondrial Actin – 2 Step around accumulation as 2011). filament involved, al., be et t actin could (Palmer shorter MID51 mitochondria is causes dimer that II overexpression interesting myosin is the its it that so regard, folded this also In are tails th the 3), Possibly, th Fig. pulls tails. (see then cytokinesis their activity yeast and by II fission membrane Myosin nodes of ER nodes. the models nm. the neighboring to to 175 at on similar attached II of assemble model, myosin are this nodes length filament to In that Several extended actin bind membranes. arrangement. dimers node on mitochondrial th Nodal individual one acts and shown around (Bii) at as ER and are assembled mitochondrion. ring the organized mitochondrion A are the both actomyosin the in that and constricting continuous depicted around filaments turn ER a Actin model filaments in both II. the together, allow bipolar constrict myosin of of to to and 4 form sufficiently INF2 membrane and the contains encircles ER 3 each in the but Step assembled at mitochondrion, mitochondrial at is INF2 the site increased II by disassemble encircle fission causes Myosin bound oligomer) enlarged completely Drp1 arrangement. Drp1 the to of myosin, Bipolar of required (actin, activity (Bi) views complex not GTPase mitochondrion. Side fission coin is 6: mitokinesis. the to ER Step during of owing models, components filaments. arrangement site, both and II actin occurs, pre-constriction myosin and process the for (purple) filame fission models at bipolar receptor membrane possible oligomerizes pre-assembled actual Drp1 from and s The OMM-bound or the 7: I binds an both dimers Step through circles) of – free constriction. ER constriction (brown of signals the in pool Drp1 to two resulting cytosolic detection): tethered network, of a the staying (coincidence from detection of thus 5 come deformation ends, might causes Step barbed filaments myosin mitochondrion. their actin recruited at underlying anti-parallel The donut) on site. (gray activity fission II INF2 the myosin with to (pre-constriction): elongate recruited and is nucleated II are Myosin (red) fission. 3: filaments mitochondrial actin of 2: Step model fission. mitokinesis The 4. Fig. A Bi ER Mitochondrion Mito 1 5 ER 2 6 + A tp1 h R(re)admtcodin(le neata h uuest fmitochondrial of site future the at interact (blue) mitochondrion and (green) ER The 1: Step (A) Drp1 – GTP GDP +Pi ? n steiiilitrcin osberlsfrsd idn in binding side 7. for Step barbed roles in the discussed Possible to are interaction. binding disassembly initial 2A), filament (Fig. the 2014) is al., side end et the to (Gurel bind filament also can of INF2 Although INF2. through membrane osrcincmlx o smoi Ircutd Typically, recruited? II pre- myosin the is into How assembles II complex. site myosin constriction fission recruitment, the actin to recruitment Following Myosin – 3 Step Bii ? 3 ora fCl cec 21)17 5946 doi:10.1242/jcs.153791 4549–4560 127, (2014) Science Cell of Journal MitochondrionMi toc h on See panelB d ? r 7 i on ER ER 4 Key ronigE n the and ER urrounding Actin filament Drp1 receptor Drp1 Myosin (dimer) (thick filament) Myosin INF2 cidence ysnI is II myosin e t.Se 4 Step nts. F.Step NF2. e htare that s a its han B Two (B) . nodes e 4553 .In

Journal of Cell Science RC)o osbyb ytncdsrpykinase-related 2014; Olson, dystrophy and myotonic (Unbekandt kinase (MRCK) Rho by MYLK), kinase possibly or chain Cdc42-binding MRLK or light MRLC as regulatory known processes, (ROCK) also myosin myosin-II-requiring Vicente-Manzanares (MLCK, by other kinase 2013; mediated In is al., and 2009). phosphorylation et assembly the al., filament of (Billington et bipolar phosphorylation activity both by motor stimulates activated which is MRLC, II myosin non-muscle COMMENTARY sebeo h M,btaanti ol eur ees of underlying could release require the nodes would 4554 this thus, again the of but and, OMM, Alternatively, case the ER on the 4Bii). assemble the (Fig. In condense ER. mitochondrion site. neighboring the would from emanating on cleavage filaments nodes assemble actin on the would activity and II nodes Myosin formin at these containing fission, nodes develops mitochondrial of II cluster Pollard, loose 2012; been myosin al., a has et which that (Lee in to model cytokinesis 2010), node-based yeast the fission able for of described aspects be uses model This principle, arrangement in Nodal the should, constriction. of of degree filament heads this the motor accommodate at myosin multiple only filament the represents thick the bipolar ingression, pre-constriction on membrane Because II limit 4Bi). partial myosin (Fig. significant the site a fission of create filament arrangement dimensions generally bipolar spatial is These II which 2B). 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II, this Because in myosin process 2012). triggers fission activate al., the of also and et kidney components (Wang in can Drp1, cells hyperglycemia ROCK endothelial to activates and response Interestingly, podocytes in (Loso 2013). and Drp1 al., fission ways et 2010). mitochondrial Strack phosphorylates several 2014; Blackstone, al., in et ROCK and Shen function 2013; Chang al., its et 2009; fission, affects by al., phosphorylation modified regulating extensively et is in S-nitrosylation (Braschi Drp1 and that ubiquitylation, known Drp1 sumoylation, phosphorylation, well is of it although modifications translational ie o iso,wihi hntigrduo eodsignal second a upon triggered certain then prime Drp1). is to (Loso of which serve (dephosphorylation might fission, state MiD51 for or sites phosphorylated MiD49 mitochondria that inactive to suggesting Drp1 its recruit MiD51 al., and causes in et MiD49 MiD51 Drp1 detector, note, (Palmer of Of mitochondria 2011). coincidence which overexpression around accumulation that which filament unclear interesting actin IMM–OMM with is is our actin, it operate although It for 2014); site would cardiolipin). contact fission al., receptor(s) the (ER for et at signals or communication accumulate [(Macdonald distinct could filaments Drp1 through the and actin stimulate results] of cardiolipin unpublished as and activity the filaments by such GTPase actin and detector, receptor Both specified Drp1 cardiolipin. sites, coincidence OMM-bound fission particular specific at the Drp1 by recruit both to mechanisms the multiple division. during partitioning from maintain to Drp1 of absence (MEFs) apart the in fibroblasts place embryonic clear pathways, mouse no areviable(Loso Drp1-null is Drp1-independent that There observation for pathway. 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Journal of Cell Science fatni iohnra iso nteimdaefuture. immediate the in fission mitochondrial role in this the actin over controversy For of actin-independent some predict 1983). and we Pollard, exist, actin-dependent could and mechanisms both Maupin because 1981; and Lehrer, reason, 2010; (Kudryashev al., populations et filament imaging low-abundance Many short for 2011). challenges imaging al., present microscopy, et electron Ydenberg especially techniques, 2010; al., et Kudryashev COMMENTARY 4558 Drubin David for MN), in-put Rochester, factual Clinic, and (Mayo advice Billadeau discussion, Dan for including: people work, many thank this to like would We Acknowledgements or presence nuclear in morphology, historically, actin and filament the common filaments actin actin been edge leading identifying have being filaments examples actin over actin-based of abundant morphology Frustrations more other amongst structures. be Drp1 overlooked might might presence easily they their reason, productive be that this For is transient. extremely template process and short membrane-based any to in filaments 2) Box for site. found fission ring the (see PD at oligomerization the plastids to similarly work plant (e.g. might signal filaments second actin a for such as and signals Finally, receptor cardiolipin). OMM-exposed Drp1 detection pathways or filaments coincidence OMM actin use an could multiple signals, and two Drp1 of on that depend mechanisms to Most likely hypothesize exist. are might fission we mitochondrial mammalian summary, In thoughts Final entse gis ormoi lse Lmuee l,2004). al., et the (Limouze classes is myosin here four note against tested Of only been 2001). has relevant al., which and blebbistatin, et inhibitor functions myosin-II-specific (Berg presumed their unknown cases are many chains in light and al., classes), myosins et 20 many the are (Korobova (over there that that II is suggest myosin message take-home general chain for A specific 2014). heavy indeed II have are myosin effects fission the could observed effects of the chain suppression 2012) However, 2014). light to) al., upon regulatory et addition al., same (Lu II the in myosin has as ours) et (or (RLC) 19 (including myosin of because DuBoff instead literature II, myosin 19 2014; the myosin in inhibited al., inadvertently studies et the (Korobova of mitochondrial in 19 some myosin of role fission, Although on a for 2009). evidence current al., no effect et is there (Quintero translocation apparent their mediates no and pathway. 2014). has al., shown II et inhibition has (Korobova study size complex one mitochondrial INF2–myosin nucleator although Arp2/3 actin pathway, an the II that the be personal INF2–myosin represent might the might complex in to this Arp2/3 Arp2/3 Karbowski, the so to pathway Alternatively, the 2014), linked al., through (M. generally alternative fission et generation (Blanchoin protein mammalian complex a force in conditions is role polymerization-based Cortactin a certain communication). evidence plays recent the cortactin Third, under of 2013). that subunits al., clearly et suggests actin-binding myosin-V-dependent yet (Murley using INF2 complex of express ERMES perhaps possibility not ERMD, do the yeast undergo budding raising mutants Second, 2010), II. V fission. myosin myosin al., and/or in First, et INF2 elongation statement. use mitochondrial this not cause support do results that Three those including exist, n su oba nmn hneaiigarl o actin for role a examining when mind in bear to issue One esol lomninmoi 9 hc id omitochondria to binds which 19, myosin mention also should We might pathway fission actin-dependent one than more Finally, Plasmodium Drosophila BlnadMlis 2013; Mullins, and (Belin ern (Pathak neurons rsh,E,Znn,R n crd,H M. H. McBride, and R. Zunino, E., Braschi, Cong, G., Benoit, O., Gribouval, B., Funalot, E., Plaisier, F., Nevo, O., Boyer, Royes, S., Karmon, H., Chung, C., H. Yang, W., D. Nowakowski, G., R., L. I. Boldogh, Hays, L., S. Karmon, D., W. Nowakowski, C., H. Yang, R., I. Boldogh, ei,B .adMlis .D. R. Mullins, and J. B. Belin, odg,I,Vjo,N,Kro,S n o,L A. L. Pon, and S. Karmon, N., Vojtov, I., Boldogh, Q., Tieu, A., Ku Mozdy, D., S., Breitsprecher, Bale, J., J., Block, E. King, M., J. 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Lake City, Storrs, Salt Iowa Utah, Iowa, New of of University, (University (Yale (University Shaw Pollard Tom Janet CA), CT), Perkins Diego, Haven, Guy San MI), California, Lansing, of Katherine East (University VT), University, Burlington, State Vermont, (Michigan of Osteryoung University, (University Rikkyo Lord Kuroiwa Matt Tsuneyoshi Japan), CA), Tokyo, Berkley, California, of (University hn,D .adRyod,I J. I. Reynolds, and T. D. Chang, C. Blackstone, and R. C. Chang, C. D. E. Chan, R. Jensen, and M. Delannoy, M., S. M. Burgess, J. Shaw, and T. H. Bui, Schlo J., E. Brown, 2388. glomerulopathy. with disease Te Charcot-Marie-Tooth C., Arrondel, H., cytoskeleton-based E. the to DNA and machinery. membranes segregation mitochondrial links Mmm1p A. L. Pon, and P. yeast. in motility mitochondrial USA actin-based A. for L. Pon, required and 3rd R., J. Yates, 1371-1381. 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Journal of Cell Science rhd,K .adLm .A. W. Lim, and E. K. Prehoda, aahda,V,Hth .L n ig,H N. H. Higgs, and L. A. Hatch, V., Ramabhadran, N. H. Higgs, and J. G. Rahme, F., Korobova, V., Ramabhadran, Kerkhoff, and D. R. Mullins, A., Quintero,O.A.,DiVito,M.M.,Adikes,R.C.,Kortan,M.B.,Case,L.B.,Lier,A.J., Bedrossian, S., Hilgert, E., M. Quinlan, o,S . o,J . asmn,M . ha,C,Akl,V,Bges T., Boggess, V., Ankala, C., Uhlar, K., M. Lakshmana, A., J. Woo, E., S. Roh, imn,A,Wge,K . ug,M n ue,U. Suter, and M. Ruegg, M., K. Wagner, A., Niemann, COMMENTARY 4560 F. Chang, and A. Boudaoud, N., Minc, A., S. A. Proctor, W. Lim, and D. R. Mullins, A., J. Scott, E., K. Prehoda, H. D. M. T. Ellisman, Pollard, and A. G. D. Perkins, T. Pollard, and S. A. J. Paul, P. Hollenbeck, and J. K. Sepp, D., Pathak, una,M E. M. Quinlan, Stojanovski, D., L. Osellame, G., R. Parton, D., K. Elgass, E. S., A. Frazier, C. S., Palmer, J., O. Koutsopoulos, G. D., Hermann, Laine, D., W., L. J. Osellame, S., Thatcher, C. 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