A 43-kDa protein related to c-Erb A alpha 1 is located in the mitochondrial matrix of rat liver.
In order to characterize Sterling's triiodothyronine (T3) mitochondrial receptor using photoaffinity labeling, we observed two specific T3-binding proteins in the inner membrane (28 kDa) and in the matrix (43 kDa) of rat liver mitochondria. Western blots and immunoprecipitation using antibodies raised against the T3-binding domain of the T3 nuclear receptor c-Erb A alpha 1 indicated that at least the 43-kDa protein was c-Erb A alpha 1-related. In addition, gel mobility shift assays demonstrated the occurrence of a c-Erb A alpha 1-related mitochondrial protein that specifically binds to a natural or a palindromic thyroid-responsive element. Moreover, this protein specifically binds to a direct repeat 2 sequence located in the D-loop of the mitochondrial genome. Furthermore, electron microscopy studies allowed the direct observation of a c-Erb A-related protein in mitochondria. Lastly, the relative amounts of the 43-kDa protein related to c-Erb A alpha 1 were in good correlation with the known mitochondrial mass in three typical tissues. Interestingly, expression of a truncated form of the c-Erb A alpha 1 nuclear receptor in CV1 cells was associated with a mitochondrial localization and a stimulation of mitochondrial activity. These results supply evidence of the localization of a member of the nuclear receptor superfamily in the mitochondrial matrix involved in the regulation of mitochondrial activity that could act as a mitochondrial T3-dependent transcription factor.
Wrutniak
C
C
Laboratoire de Différenciation Cellulaire et Croissance, Institut National de la Recherche Agronomique (INRA), Montpellier, France.
Cassar-Malek
I
I
Marchal
S
S
Rascle
A
A
Heusser
S
S
Keller
J M
JM
Fléchon
J
J
Dauça
M
M
Samarut
J
J
Ghysdael
J
J
D000345:Affinity Labels; D000818:Animals; D001483:Base Sequence; D002458:Cell Fractionation; D003429:Cross Reactions; D004272:DNA, Mitochondrial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008297:Male; D016253:Microscopy, Immunoelectron; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D014018:Tissue Distribution; D014284:Triiodothyronine / Q000378:metabolism*
D000345:Affinity Labels; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D014284:Triiodothyronine