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TItE JOURNAL OF BIOLOGICAL CHEMISTRY (en rev¡oén)
Ca
2 /CM-PKII aurapbospbarylation. AcLivated Ca2~/CM-
PKII would pbospitarylate cytoskelotal camponents,
perbaps cytokeratins 8 arad 18, tbereb>’ disrupting puliarive
irahibitor>’ irateractiaras boliweara libe cytoskaiotora and CPT-I.
StimulaLion of CPT-! upan disruptian of libo cytoskolaton
would be also acbievod b>’ challenga of intact bepaLocyres
lio IDPN or b>’ Lrealimenli of permeabilized bepaliocytes witb
trypsla ira mild coradiliions. Stabilization of libo cyroskalaton
wilib Laxol ma>’ provarat tite malorayi-CaA-indopendent aculio
stimulaLian of CFI’-I.
It is obvious ritat libe raotion tbat fatr’y acid traraslocation
lato mitochondria ma>’ be controlad it>’ madulation of libe
irateractioras botweera CFI’-I arad cyraskeletal componenlis
(i.e. by a malara>’l-CoA-iradeporaderat mechanism) does raoli
diminisb Lite imporlianca of maiorayl-CoA as a pitysiolagical
madulator of CPT-I activir>’ (5,8). Ora ono barad, since libo
pioneering work of McGarry arad coworkers (8,43), citarages
la long-chaira fality acid oxidation urader man>’ diffarerat
patbo-pbysiolagical situatioras bayo boen sbown La be liraked
Lo changos ira iratracellular malonyl-CoA concentration
and/or citaragos ira tite serasitivit>’ of CPT-I Lo ma]ora>’l-COA
(1,2,5). On Lite aLbar batid, several observatioras suggesli libali
malonyl-CoA-depondorat arad malarayl-CoA-iradeperaderat
aculie control of bepatic CP’I’-I activir>’ migbt aperate in
coracerli. First, Wc itave rocenLí>’ showra libat stimulatian of
Lite AMP-activated proteira kinase -a majar protela kinasa
¡ravolved la libe control of bepatic lipid metabolism- laads to
ara acrivation of bepatic CPT-I by ma]on>’l-CoA-dependont
arad malon>’l-CoA-indapendent mocitanisms (44). Second,
a fractiara of bapaLic acatyl-CoA carboxylase, tite arazyme
resparasiblo for libe s>’rathosis of malon>’l-CoA, has beon
reconlil>’ suggoslied Lo be bound ta Lbo cytaskoletan (45).
Third, ir itas beon puÉ forward titar libe 280-KDa isoform of
aceLyl-CaAcarbox>’lase migbL interact witb libe outer leafler
of tbe mitocitoradrial autor membrana ira order Lo citannel
malon>’l-CoA for CP’I’-I initibition (46). Fourtb, tite rocent
obsorvation libar Lite bulk of tite CPT-I protein seems Lo
face libo cytoplasmic sido of Lite mitocitandrial auter
membrane (29) makes more Iikel>’ LitaL interactiaras
beliwoon CFI’-I arad cytoskeleta] camparaerat; migbt occur.
Ira tbo conten of tbe emergirag role of cytoskelolial
filamentaus raoNrorks la intracelular sigraaling (47), currarat
resoarcb ira our laboratorios is focussed ora Lito possible
axisrenca of a coardinalie control of CPT-! arad acet>4-CoA
carbax>’lase activities by modulation of interaction; between
tite cylioskoletora and libe mitochoradrial autor membrarae.
.4cknow/edgements - Wa are iradetited to Dr. Ismael Gaiya arad
Ms. Teresa Gómez del Pulgar for expart techaical asistarace, as
well as Lo Dr. Alejandra Alonso arad Dr. Jean Eraracois Leterrier
for ha¡pfuL critical commerats.
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