The human steroidogenic acute regulatory (StAR) gene is expressed in the urogenital system and encodes a mitochondrial polypeptide

TY - JOUR

T1 - The human steroidogenic acute regulatory (StAR) gene is expressed in the urogenital system and encodes a mitochondrial polypeptide

AU - Gradi, Alessandra

AU - Tang-Wai, Richard

AU - McBride, Heidi M.

AU - Lee Lee Chu, Lee Chu

AU - Shore, Gordon C.

AU - Pelletier, Jerry

N1 - Funding Information: not shown))a ndp rocessetdo a maturef orm ~ 3 to 4 kDa smallert hanthe precurso(rt op panel, lane 3). The import of StAR into the mitochondriwa as found to be dependent on the presenceo f an electrochemicaplo tentia(l i.e., was inhibitedb y CCCP, comparel ane 4 to lane 3) and was temperaturdee penden(tc omparela ne 6 to lane 3). The exact role of StAR in regulatingt he import of cholesteroils not well defined. StAR may directly bind cholesteroal nd co-transporitt into the mitochondriaml a-trix. A more likely role may be to regulatea ctivityo f other transports ystemst hat are directly involvedi n cholesterol mobilizationw ithin the organelleT. he fact that import of StAR requireda n electrochemicpaol tentiala crosst he inner membranseu ggesttsh atStAR must localizet o internal compartmentws ithin the organelle,c onsistentw ith the observedp rotectiono f the processedS tAR againste xoge-nously added trypsin (Fig. 4, top panel, lane 3). The processedp roductw as extractablew ith alkali (pH 11.5), indicatinga soluble protein (data not shown). The previously characterizemd atrix protein pOCT \[12\]s hows a patterni denticalt o that of hStAR (Fig. 4, bottomp anel) which suggestsa matrix localizationa; lthoughw e cannot formally rule out an intermembranloec alizationW. e feel this latter possibility to be remote since the signal se-quenceo f StAR (Fig. 2) resembletsh atof a typicalm atrix protein rather than an intermembranesp ace protein \[9,13,14\]. Our resultsa re consistenwt ith the notion that therea re at least two facets to the transporto f cholesterowl ithin mitochondriaO.n e of thesei ndicatesa directr ole for StAR in regulatingt his transport-as suggestedb y mRNA expressionle vels in testesa nd ovaries( Fig. 3) and of the associationo f StAR germlinem utationsw ith lipoid CAH. The other facet implies a StAR-independenttr ansport mechanismg,i venthe absenceo f StAR mRNA in steroidogenic tissuess uch as placentaa nd brain. A putativer ole for StAR in cholesteroml etabolismin the kidney is sug-gestedb y the novel finding that StAR mRNA is abun-dantlye xpressedin this organ( Fig. 3). A.G. and R.T.-W. contributede qually to this work. A.G. is a recipienot f a fellowshipf romthe IstitutoP asteur FondazioneC enci Bolognetti.W e thank Dr. Nahum So-nenbergf or critical readingo f the manuscripat nd for his supportd uringt hec ourseo f this work. We thankD rs. Karl H. Scheita ndHeinz yon der Kammer( Max-Planck-Institut fffr BiophysikalischeC hemie) for a kind gift of their human cDNA library. A.G. thanks Drs. R. Viger and H. Imatakaf or helpful suggestionsJ..P . is an Medical Re-searchC ouncils cholar.T his work was supportebdy grants from the Medical ResearchC ouncilof Canadat o G.S. and J.P.

PY - 1995/10/5

Y1 - 1995/10/5

KW - (Human)

KW - Mitochondrion

KW - Sequence analysis

KW - Steroidogenic acute regulatory protein

KW - cDNA

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UR - http://www.scopus.com/inward/citedby.url?scp=0029112452&partnerID=8YFLogxK

U2 - 10.1016/0005-2760(95)00140-8

DO - 10.1016/0005-2760(95)00140-8

M3 - Article

C2 - 7548191

AN - SCOPUS:0029112452

SN - 0005-2760

VL - 1258

SP - 228

EP - 233

JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism

JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism

IS - 3

ER -