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iohnra pgntc,Ncerpores Nuclear , Mitochondria, droplets, Signaling, modification, Post-translational arnR awo*adJh .Hanover* A. John and Harwood* R. Katryn Nutrient-driven COMMENTARY ß Atosfrcrepnec [email protected];[email protected]) ([email protected]; correspondence for *Authors Health, of Institutes National USA. NIDDK, 20892-0851, , MD Molecular Bethesda and of Laboratory , of pair single and (OGT) of a removal by and addition governed dynamic termed The by 1984). been Hart, residues their has of group modification hydroxyl and the at modified are of Hundreds Introduction WORDS: KEY and residues) threonine and serine to physically of acetylglucosamine of establishment global the gradients through that to is suggests defined achieved response is evidence this in Mounting way availability. one manner nutrient regulated in changes spatiotemporally behave machinery a cellular that in requires functioning cellular Proper ABSTRACT yln odsrt nrclua ie,tu loigte oestablish to anchor them OGT allowing to thus functions, sites, domains intracellular catalytic Recent discrete multifunctional to their their cycling substrates. to use must addition OGA they in and where that of suggest locations hundreds reports cellular recognize discrete to selectively targeted variants are protein producing that spliced, alternatively are the genes the both MGEA5) genes: and of (OGT) pair single transferase a by of encoded are state for removal nutritive responsible this the enzymes The upon pathway, . inform an to signaling poised uniquely hexosamine is modification nutrient-responsive the on Because turnover. GlcNAc nntin supply. nutrient alterations in global to responses spatiotemporal such, functioning, proper ensuring As in of role proteostasis. enzymes mitochondrial the and of expression tethering remodeling, the gene of droplet control epigenetic lipid signaling including targeted and by established O gradients signaling localized The deacetylase, activities. of gradients a enipiae navreyo ies tts including states, disease diabetes of and variety cancer a neurodegeneration, of disease, in Deregulation al., cardiovascular are implicated et 2012). they been (Shafi the al., (OGA) has where for et adulthood to or types, Yang stage (OGT) 2000; tissue fetal development the all from vertebrate transition in either expressed for OGT Both necessary are 1997). al., OGA et Lubas and 1997; al., et (Kreppel respectively GcA yln nlec ayipratclua processes, cellular important many influence cycling -GlcNAc 04 ulse yTeCmayo ilgssLd|Junlo elSine(04 2,15–87doi:10.1242/jcs.113233 1857–1867 127, (2014) Science Cell of Journal | Ltd Biologists of Company The by Published 2014. b - N O aeyguoaiiaeC(-lNcs;OGA), (O-GlcNAcase; C -acetylglucosaminidase -GlcNAc, O GcAyain( -GlcNAcylation O GcAyain -GlcNAcylation, O O GcAyainlvl r dependent are levels -GlcNAcylation GcAae(G,as nw as known also (OGA, -GlcNAcase O O GcA yln per opa a play to appears cycling -GlcNAc O GcAyain(orsand (Torres -GlcNAcylation GcA yln hn lblybtatlocally act but globally think – cycling -GlcNAc N aeyguoaie This -acetylglucosamine. O O lne diinof addition -linked O GcA transferase -GlcNAc GcA diinand addition -GlcNAc O GcA cycling -GlcNAc O GcA is -GlcNAc O O -GlcNAc -GlcNAc O N - - pcfcbnigprnr httte hmt rcs intracellular precise to with OGT them and tether propose or OGA that we of partners low interaction field, binding by the specific achieved very in UDP-GlcNAc be could findings of of this recent that conditions conditions on under Based under or homeostasis. UDP-GlcNAc, both high which important very levels, UDP-GlcNAc be in global changes would to a mechanism response cellular in fine-tuned local more influenced protein a govern be 2A, Concurrently, might Fig. 2A). might in (Fig. outlined proteins manner those of as that such GlcNAcylation is modulate conditions, possibility to certain One OGT under responses. and spatiotemporal OGA specific the between of highly achieved functions is balance competing growth. a how cell apparently to and as cell storage remains in question nutrient are The reduction of that a attenuation processes as and augment such proliferation to conservation, cell nutrient the with ‘direct’ associated to intended is that O achieve regulated. and tightly substrates and be their OGT must that recognize specificity ensure to that able factors are the OGA 2012), Zachara, Ngoh 2011; 2010; al., al., et deregulated Hart et 2013; with Hanover, and associated (Bond are cycling GlcNAc states at cell specific disease either in Because OGA or types. OGA, times, and specific OGT and during locations, of OGT cellular partners specific interaction of different localization the subcellular and the levels, GlcNAc pattern specific protein to The of modified responses. cellular are downstream substrates proper specific ensure which by exist pathways many aayi mO) hc c ssnoso nrycag and charge energy of sensors as of act target which mammalian proteins (mTOR), and signaling acid the (AMPK) rapamycin join kinase amino HBP protein the activated the of AMP enzymes as the the regard, uridine. such this and In of glucose nutrients, (acetyl-CoA), UDP-GlcNAc state A from acetyl-coenzyme into , nutritional derived feed making the are that HBP, components synthesis reflect the key to Specifically, of cell. ideal product 1). addition (Fig. final 2010) GlcNAc the al., is diphosphate et uridine (Slawson (UDP-GlcNAc), OGT, levels of ATP substrate and The , biosynthetic fatty to sensitive acid, hexosamine is pathway the This (HBP). pathway termed pathway 2010; al., nutrient-sensing et Ngoh 2011; al., et 2012). Hart Zachara, 2013; Hanover, and (Bond ua ee NleadMle,20;Saie l,2000). al., et shown been Shafi have functions 2002; of protein be range of Muller, a to pair with , and single proteins proteins of a (Nolte Hundreds and of from products genes the removed human by and performed different is , to GlcNAcylation many added protein is by unlike phosphate whereby However, phosphorylation. respectively. levels, acid amino GcA oiiaino rti ol ntaeacascade a initiate could protein a on modification -GlcNAc wn oisntin eedne h rsneo bec fan of absence or presence the dependence, nutrient its to Owing O O GcA eaoimi ieyblee ob ato a of part be to believed widely is metabolism -GlcNAc GcAyaini fe osdrdt eaaoost protein to analogous be to considered often is -GlcNAcylation O GcAyae Cpln ta. 08,sgetn that suggesting 2008), al., et (Copeland -GlcNAcylated O GcAyaini h eli eemndi atby part in determined is cell the in -GlcNAcylation O GcAyaint nuebt lbland global both ensure to -GlcNAcylation N -acetylglucosamine 1857 O O O O O - - - - -

Journal of Cell Science COMMENTARY eiuso ltoao G n G agt,alw o h euaino motn ontemclua rcse nantin-eedn anr T manner. nutrient-dependent a in processes cellular downstream important 1858 of regulation the for brackets. allows in targets, nuc given OGA acid, amino are and OGT carbohydrate, involved pathway. key of enzymes of biosynthetic plethora UDP-GlcNAc. metabolism a hexosamine substrate the OGT the of with the of residues intake, produce overview nutritional to an including components, – inputs, acid physiological UDP-GlcNAc extracellular substrate, many OGT integrates the (HBP) of Generation 1. Fig. O GcA yln,tednmcadto oadrmvlof removal and to addition dynamic the cycling, -GlcNAc ora fCl cec 21)17 8716 doi:10.1242/jcs.113233 1857–1867 127, (2014) Science Cell of Journal h eoaieboytei pathway biosynthetic hexosamine The O GcA nsrn rthreonine or serine on -GlcNAc etd n fatty and leotide he

Journal of Cell Science COMMENTARY pcfcrsosst D-lNclvl Fg B.Sc a about information Such translate and 2B). to (Fig. sensitive cell levels the for allow UDP-GlcNAc allowing would to distance, mechanism tethered responses increasing the to OGT with specific close or are ‘off’ OGA proteins activity target of or enzyme the gradient activity: when of ‘on’ local enzyme localized threshold is This other a evoke establish 2005). for therefore al., might past to et the Pratt them in 1997; reported allow been (Go systems to has as responses, or locations consequent spatiotemporal with specific levels, responses. highly UDP-GlcNAc cellular for overall allow the that to activity ‘cloud’) responses protein gray of the gradients by protein introduce (illustrated of potentially gradients at thus OGT local and or establish GlcNAcylation, OGA could of locations tethering cellular The specific (B) responses. cellular subsequent downstream and protein levels total UDP-GlcNAc in intracellular changes in changes UDP-GlcNAc global in with changes to responses local levels. and Global 2. Fig. A h elcnrsodt eti xrclua hsooia inputs physiological extracellular certain to respond can cell The (A) rihe l,19;Gifne l,21;Iarad tal., et Izaurralde 2011; al., et Griffin 1996; al., et ¨rlich O GcAyainlvl omdlt proper modulate to levels -GlcNAcylation O - inln ahas ihrgntclyo hog altered through these or states. of disease certain deregulation genetically in result the might either conditions, how nutritional pathways, upon touch signaling cellular and maintain by protein mechanisms metabolism to of the modulation means examine the will which into a status we nutritional as Furthermore, in homeostasis. responses changes into translate metabolic to insight of able distinct variety provide is wide cell can the a information how with This undergo components. well they as cellular interactions OGA, and specific OGT the of isoforms as different the of properties the and in in elsewhere transduction not signal but cells. serum-stimulated Cos7 nucleus, following and cytoplasm, membrane plasma in the increase 2011). rapid a al., observed the colleagues et and (Carrillo Carrillo Specifically, dynamics compartment-specific that exhibit spatiotemporal suggested the stimuli in inducing changes the resonance detect of fluorescence cellular to dynamics using in (FRET) study transfer changes energy specialized a highly Interestingly, into responses. state nutritional the oansrcueadlclzto fOTadOAisoforms OGA and OGT of localization and structure Domain A oan hra G- ak hsdmi n nta otisa contains extension. instead and C-terminal putative domain long a this 15-amino-acid possesses lacks unique OGA, OGA-L OGA-S of C-termini. whereas isoforms their domain, splice at HAT two differ The OGA-S, N- (B) and variable domains. OGA-L possess catalytic sOGT, identical and but structure. mOGT termini ncOGT, domain OGT, and of isoforms isoforms OGA splice and OGT 3. Fig. The 2011). al., the et been of Sakaidani is also 2012; isoform has al., ncOGT et (eOGT), (Sakaidani OGT with described extracellular enzyme 2000). activity, unrelated al., genetically transferase et Shafi a 2002; recently, Muller, and More a Nolte localization 2003; as al., nucleocytoplasmic well et as shows (Hanover 2003), that al., (sOGT) X et isoform (Love the short (mOGT) (ncOGT) mitochondria on nucleocytoplasm the the to found and to identified, localize been is that have isoforms isoforms OGT including spliced OGT alternatively distinct for several encoding and coding transcripts 2000), al., gene et (Shafi the mammals, In O GcA transferase -GlcNAc nti omnay ewl rsn ndti h localization the detail in present will we Commentary, this In O GcAyaino RTbsdsno pcfclyat specifically sensor FRET-based a of -GlcNAcylation ora fCl cec 21)17 8716 doi:10.1242/jcs.113233 1857–1867 127, (2014) Science Cell of Journal OGT ee(aoe ta. 03,weesmG is mOGT whereas 2003), al., et (Hanover gene O GcA oiiaini epnet signal- to response in modification -GlcNAc , 1 D n secddb l 3exons 23 all by encoded is and kDa 116 O O GcA yln osi fact in does cycling -GlcNAc GcAyainatr cellular alters -GlcNAcylation A h three The (A) O -GlcNAc 1859

Journal of Cell Science uh u icsino G ilfcso h iiaiisand similarities the As on 2011). focus al., less will et OGT been of (Sakaidani has discussion homology our apparent it which such, to no system; isoforms, exhibits OGT endomembrane three it the the than performs characterized in extensively but 3A). UDP-GlcNAc function (Fig. utilizes 2000) its al., eOGT et described Shafi newly 2002; Muller, The and Nolte 2003; al., et is sOGT and , COMMENTARY tutrssgetta G rmtsctlssuigan using This 1860 2012). al., promotes et (Lazarus These OGT 2012). endocyclic mechanism al., that migration et the electrophilic (Lazarus suggest sulfur which UDP- by hydrolyzed structures replaced in slowly is crystal atom UDP-5SGlcNAc, very oxygen bound, a analog, substrate using complex peptide GlcNAc solved ternary modified the were and al., examine structures et UDP To (Lazarus 2012b). both determined al., with of be et identity to Schimpl the remains 2011; the including , whereby although transfer, catalytic substrate, glycosyl the action protein of OGT the mechanism a to exact for proposed prior mechanism co-workers binds substrate UDP-GlcNAc kinetic and peptide structures bi-bi crystal Lazarus for these between sequential experiments, on site Based rotation kinetic active cleft 2011). hinge-like and al., the wide et a opening a (Lazarus through binding 13, substrate, formed and peptide in TPR12 be and OGT of to this UDP structure stabilize appears both the to In ‘latch’ with 2011). a a complex al., as and et acting 11 (Lazarus domain ‘closed’ and conformation catalytic a TPR10 the adopts of between OGT helix alone, interactions UDP with with complex conformation, solved a and demonstrated been in UDP have when have OGT structures with that analogs These alone, 2012). of donor Vocadlo, UDP sugar in structures with (reviewed with complex or crystal a substrate several in peptide are and that identical, variants been is has isoforms isoform OGT 2000). each Hanover, and in different (Lubas the among isoforms domains specificity substrate the the TPR modulate in to differences suggested the the of Consequently, not 2006). length al., is OGT et motif Lazarus of sequence 2003; variety substrate La a and specific (Blatch apparent for a specificity although substrate substrates, determining in role (Jı importin- the an to (Blatch resemblance residues with Asn superhelix with a La lined and is as that exists of groove and domain center and TPR amphipathic crystallized The ncOGT motifs been 2003). Specifically, 9.5 al., has et 1999). has ncOGT (Hanover motifs mOGT al., 2.5 whereas et only motifs, sOGT Liu TPR 2003; 12.5 Yanagida, al., possesses and et (Goebl interactions Iyer protein–protein 1991; in to thought role are a that each, have repeats TPR acid 12.5 amino 34 and 2.5 of consisting between a motifs, contain also and isoforms domains, The possesses TPR 2003). their al., in et mOGT differ (Love domain example, TPR the of region For upstream N-terminal variable its N-termini. in sequence sequence unique mitochondrial-targeting variation and Each length their and the 3A). in domain, (Fig. of primarily 1997) catalytic occurs isoforms al., identical the et between an Lubas al., possesses 2011; et al., (Kreppel isoform region et catalytic Lazarus multidomain a 1997; a domain, a and (TPR) include region that repeat linker regions tetratricopeptide into and divided N-termini be variable can isoforms OGT spliced sOGT. and mOGT ncOGT, between differences ´ 0 D n secddb xn o2 Lv ta. 2003), al., et (Love 23 to 5 exons by encoded is and kDa 103 e ta. 04.Tecaatrsiso hsgov ih aea have might groove this of characteristics The 2004). al., et nek ngnrl h tutrldmiso h he differentially three the of domains structural the general, In smnindaoe h aayi oano l he OGT three all of domain catalytic the above, mentioned As sl,19;Jı 1999; ¨ssle, , 8kaadecddb xn 0t 3(Hanover 23 to 10 exons by encoded and kDa 78 ´ e ta. 04.TeTRdmi er some bears domain TPR The 2004). al., et nek sl,19;Hnvre l,20;Ie tal., et Iyer 2003; al., et Hanover 1999; ¨ssle, a aiyo ula rnpr receptors transport nuclear of family oue ndtriigtefcosta r motn for important the are of determination that including factors OGA, a by the catalytic via recognition determining key proceeds substrate on and have two studies Asp175, focused Additional requires mechanism. and substrate-assisted 2005b; OGA-L Asp174 two-step al., catalytic residues, the human et that aspartate Macauley suggest in studies 2005a; These al., mechanism 2007). et al., et Macauley Whitworth 2009; al., et aau ta. 03.I sntytceri hr r te substrates other OGT. are by there cleaved if clear be yet might not cleavage 2011; is that Hanover, It the 2011; 2013). al., al., during and et et Daou Lazarus co-substrate occurs 2011; al., a et (Capotosti protein as reaction where used out site UPD-GlcNAc carried active being with HCF-1 same of the cleavage in proteolytic with the HFC-1, cell in recent involved of the is Interestingly, maturation OGT 2010). of that al., demonstrated stages have et stably reports Mazars different two 2011; regulate (Hanover, generate cycle that to event fragments processing associated proteolytic UDP- undergoes unusual that regulator for an are epigenetic conserved observed evolutionarily which an affinities is OGT, of of range center 1 wide the global (from active the GlcNAc that cause the to in suggesting likely in reflected 2012), is changes al., substrates protein structural et different (Lazarus of interaction binding large substrate the is that interface demonstrates also complex ternary Cmes ta. 01 ekle l,19) lentv gene short Alternative a 1998). and (OGA-L) al., isoform long et a isoforms, Heckel two humans yields 2001; in splicing 10 al., chromosome on (MGEA5), et located 5 (Comtesse is OGA antigen encoding gene meningioma-expressed the as identified First O-GlcNAcase ehnsi tde htuetehmnvratadsynthetic on and and (C 2006) variant inhibitors al., homologs human et and bacterial the Rao substrates 2010; use of al., OGA that et studies studies He structural 2006; mechanistic al., on et OGA based of (Dennis mechanism been catalytic the has understand to work successful, intact an in is activities it relative although their 2009), cell. reflects Vocadlo, this and whether Macauley unclear 2006; In al., OGA-L 2008). than et activity al., (Kim enzyme lower et exhibits is OGA-S (Butkinaree that N- experiments, site the cleavage 3 between during caspase 677- region cleaved a truncated linker contains a domains a as C-terminal produced OGA-L, and is In OGA-S species. result, (Comtesse a amino-acid OGA-L As 10 to 2001). exon relative extended al., codon an et stop to alternate leading an skipped, utilizes is that 11 intron the of of 16 site variant by splice splice al., encoded a et is is (Gao OGA-S product OGA-L protein 2001). 2004). 916-amino-acid 2008; al., unclear a al., produces et is and et Toleman exons, (Butkinaree it 2014; HAT al., domains, a et as HAT He functions known protein the to of whether al., C-terminus 15- similarity known unique isoform OGA-L the et a Despite the to has (Comtesse OGA-L extension. OGA-S whereas C-terminal similarity domains 2002), amino-acid-long The Pils, (HAT) with and Schultz 3B). transferase 2001; extension (Fig. but isoforms acetyl C-terminal domain, C-termini Both a hyaluronidase their 2011). contains N-terminal at lipid-droplet-associated identical al., differ and the an et exhibits 2001) possess OGA-S in (Keembiyehetty al., whereas predominantly et localization 2001), found (Comtesse al., nuclear et is (Comtesse OGA-L cytoplasm (OGA-S). isoform nadto,tecl yl euao otcl atr1(HCF-1) 1 factor cell host regulator cycle cell the addition, In eas fot ocytliehmnOAhv o e been yet not have OGA human crystallize to efforts Because ora fCl cec 21)17 8716 doi:10.1242/jcs.113233 1857–1867 127, (2014) Science Cell of Journal m ooe 20 over to m m )(hne l,2012). al., et (Shen m) ¸etinbas OGA ta. 06 Greig 2006; al., et ¸ eeweente5 the wherein gene nvitro in 9

Journal of Cell Science oe loigtepsaeo agrmlclsntpritdpirt Nup98 to prior permitted not molecules larger of passage the allowing pore, niiulaioai iecan perntt lyarl in role a play peptide The to the not 2012a). appear al., and chains et sugar side (Schimpl acid the substrate amino protein both individual or the protein and 2012), of the al., OGA backbone on et sugar (Shen between the recognition contacts and OGA al., that OGA modulate suggest et between that studies these substrate Schimpl contacts of either 2012a; results is The that al., it 2012). substrate al., et the et (Schimpl Shen of 2010; features catalysis the to and contribute involved OGA of residues COMMENTARY ope ihbt uoaBadtepopaaeP1 thsbe hw httelclzto fOTi hscmlxi eedn nArr .Teepisof pairs These dau B. into Aurora partitioning on protein dependent proper is ensure complex to this manner in remodeling. OGT complex pore tr of presumably Nuclear a localization a in (E) the in found cytokinesis. that activities are shown of their OGA been completion and coordinate has OGT and somehow It both activities PP1. cytokinesis, phosphatase opposing During TRAK the Cytokinesis. with and (D) via enzymes B fusion. binding, Aurora mitochondrial TRAK promotes both and with through effect complex directly TRAKs this either to reverses OGA binds potentially OGT of OGT networks, fusion. Overexpression trafficking. and Mitochondrial or (B) fission remodeling. Mitochondrial droplet along (C) lipid mitochondria in of resulting proteins, trafficking localized the surface of of degradation removal the the increases in results droplets lipid 4. Fig. insight regulated provide nutritionally might a interactions in interact these to substrates Identifying them allow protein manner. to likely specific physical are and regulated with isoforms patterns differential highly these localization the a of specific properties in for the substrates means Further, protein a manner. various specific provide the of of isoforms characteristics recognition OGT unique the and that OGA likely is it targeted Overall, of effects spatiotemporal The recognition. and binding substrate O GcA yln n oaie ellrremodeling. cellular localized and cycling -GlcNAc O GcA rmtepoesm n t usqetatvto.Poesmlatvto ttesraeo ii droplets lipid of surface the at activation Proteasomal activation. subsequent its and proteasome the from -GlcNAc O GcAyae R1adOA idctdb h elwsa) hc eut nicesdmtcodilfission. mitochondrial increased in results which star), yellow the by (indicated OPA1 and DRP1 -GlcNAcylates O GcA cycling -GlcNAc O GcAyaino u9 yOT(elwsa)cnrlxte‘iv’lk tutr ftenuclear the of structure ‘sieve’-like the relax can star) (yellow OGT by Nup98 of -GlcNAcylation A ii rpe eoeig h agtdlclzto fOASb eiii- ttesraeof surface the at perilipin-2 by OGA-S of localization targeted The remodeling. droplet Lipid (A) O -GlcNAcylation. icse below. targeted achieved discussed of be examples Specific cannot factors. O homeostasis genetic or cellular the when dietary for maintain to arise owing explanation status that to an nutritional states offer order its disease might in communicate they responses to Moreover, homeostasis. able appropriate is elicit cell and the how into xesv ii trg nlpddolt a elne othe to better linked A be atherosclerosis. can and droplets diabetes lipid obesity, in of because storage development interest garnered lipid has study excessive their Furthermore, Guo homeostasis, 2009). in cellular (reviewed al., beyond of et and aspects metabolism originally energy various and were lipid in including players droplets key Lipid as storage have emerged they recently, . the more however, organelles; inert for neutral be to considered responsible of organelles hydrolysis cellular and are droplets Lipid and perilipin-2 proteasome OGA-S, the – remodeling droplet Lipid GcA yln n h usqetclua epneare response cellular subsequent the and cycling -GlcNAc ora fCl cec 21)17 8716 doi:10.1242/jcs.113233 1857–1867 127, (2014) Science Cell of Journal O GcAyain rboth. or -GlcNAcylation, n a oein role a has and he cells ghter ansient 1861

Journal of Cell Science iohnra oiiy Wlse l,20) Because 2003). al., et modulate to (Wells substrates, for mobility) mitochondrial of necessary mitochondrial availability status are nutritional the communicate might the that (i.e. proteins that regulatory nutritional possible those of of UDP- is state number it including of a function, levels mitochondrial 1), from the (Fig. input As by factors). pathways influenced complexes are and transcriptional GlcNAc II of (i.e. to OGT, Pol components regulation machinery OGT RNA with transcriptional localized modify target could interaction in it also where role its might a through OIP106 to trafficking addition mitochondrial in that, authors The suggest complex. ternary RNA-Pol-II–OIP106–OGT a forms 07 odse l,19) nadto,i skonta the that known is it Brasaemle, addition, 2009; lipid In al., in 1999). with et al., involved et colocalizes (Bickel actively Londos be 4A) it (Fig. 2007; to where formation known droplets, droplet protein lipid a nascent perilipin-2, of surface metabolism. energy insight and further lipid which provide of regulation will by the remodeled into mechanism and formed dynamic are and droplets lipid complex the of understanding COMMENTARY 1862 II) Pol with (RNA interacts II OIP106 that polymerase 4B). shown RNA (Fig. have and 2003) TRAKs OGT al., Iyer both the both et alters (Iyer experiments, of al. or co-immunoprecipitation roles et kinesins, or using recruitment Miro and Interestingly, to function OGT and recruit the to (Brickley to TRAK TRAKs that possible found the Grif-1) therefore is been It as 2003). al., have TRAK2 O et known (Iyer interestingly, and OGT to which, bind also humans) kinesin-binding 2011), humans, in the Stephenson, (OIP106 includes in also TRAK1 (OIP98 complex proteins This Stowers adaptor 2002). 2005; al., al., et (Guo et Milton Miro protein GTPase kinesin-binding Chan, Rho the mitochondrial and and the (Detmer often containing complex distances mitochondria protein long where over neurons, In transported 2007). in be as to well particularly regulation need the as is for apoptosis, 2004), trafficking and of development Bliek, mitochondrial embryonic der of during van important regulation and Rube the 1995; microtubule and 2000b; Hollenbeck, and Steward, and and actin Ligon Morris 2000a; both Steward, and along (Ligon networks trafficked kinesins are and TRAKs Mitochondria the Miro, OGT, – trafficking Mitochondrial metabolism. uniquely lipid cell OGA-S and the carbohydrate with which link mobilization, to by and suitable droplet mechanism storage lipid a regulating lipid in is regulates role this a Potentially, a have the could maturation. be and that activity might OGA-S proteasomal of there droplets the level between that lipid in system suggesting with feedback results 2011), associated complex al., levels are et been that OGA-S (Keembiyehetty has proteins of it of Moreover, reduction stabilization protein surface. and that droplet activity lipid demonstrated proteasomal the in droplet, on increase lipid remodeling local the a surrounding in could the area resulting lipid droplets immediate of the lipid removal by in of high proteasome the surface enhanced a the to 2006). 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