Gene, 119 (1992) 307-312 0 1992 Elsevier Science
GENE
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Differential expression of genes specifying human cytochrome c oxidase (Mitochondrial protein; ysis; muscle; liver)
nuclear
gene; respiratory
chain;
electron
two isoforms of subunit Via of
transport;
recombinant
Gian Maria Fabrizi a*, James Sadlock a, Michio Hirano a, Shuji Mita”“, Rosario Rizzuto a*, Massimo Zeviani b and Eric A. Schon aTc
DNA;
nucleotide
Yasutoshi
sequence
anal-
Koga a,
H. Houston Merritt Clinical Research Centerfor Muscular Dystrophy and Related Disorders. and Departments of” Neurology and ’ Genetics and Development, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; and h Istituto Neurologico C. Besta. Via Celoria 11, Milano, Italy. Tel. (39-2)236-2451 Received
by J. L. Slightom:
16 December
1991; Revised/Accepted:
28 March/6
April 1992; Received
at publishers:
25 May 1992
SUMMARY
Subunit Via of mammalian cytochrome c oxidase (COX; EC 1.9.3.1.) exists in two isoforms, one present ubiquitously (‘liver’ isoform; COX Via-L) and the other present only in cardiac and skeletal muscle (COX Via-M). We have now isolated a full-length cDNA specifying human COX Via-M. The deduced mature COX Via-M polypeptide is 62% identical to the human COX Via-L isoform, but is approximately 80% identical to the bovine and rat COX Via-M isoforms, suggesting that the two COX Via isoform-encoding genes arose prior to the mammalian radiation. Transcriptional analysis showed a tissue-specific pattern: whereas COXVIa-L is transcribed ubiquitously, COXVIa-A4 is transcribed only in heart and skeletal muscle. The cDNA specifying COX Via-M is a prime candidate for use in investigations of Mendelian-inherited COX deficiences with primary involvement of muscle.
Cytochrome c oxidase (COX), the terminal electron carrier of the mitochondrial respiratory chain, is composed of subunit polypeptides encoded by both nuclear and mitochondrial DNA. The three largest, mtDNA-encoded, subunits (I, II and III), perform the catalytic function, but the
ten smaller nuclear-encoded subunits (IV, Va, Vb, Via, VIb, VIc, VIIa, VIIb, VIIc and VIII; nomenclature of Kadenbath et al., 1983b) play an unknown role. The different kinetic properties of isolated COX from bovine liver and heart suggests that the latter modulate the activity of COX by optimizing the enzymatic activity to the metabolic requirements of different tissues (Merle and Kadenbach,
Correspondence to: Dr. E.A. Schon, Columbia
Abbreviations:
INTRODUCTION
sicians and Surgeons,
Tel. (212) 305-1665; Fax (212)305-3986. * Current addresses: (G.M.F.) Istituto Policlinico
La
Scotte,
Tel. (39-577)290672; mamoto University Tel. (81-96)344-2111; versita di Padova, Tel. (39-49)828-6569.
University
College of Phy-
630 W. 168th St., New York, NY 10032, USA.
Universita
di
di
(S.M.) First Department Medical School, l-l-l (R.R.) Department
Scienze
Siena,
53100
of Internal
of Biomedical
Via Trieste 75, 35121 Padova,
Italy.
Neurologiche,
gene encoding
Siena,
COXVIa-M, gene encoding
Medicine,
Honjo, Kumamoto
aa, amino acid(s);
Italy. Ku-
860, Japan.
Sciences,
Uni-
bp, base pair(s);
COX, cytochrome
c
oxidase; COX, gene (human, bovine) coding for COX; Cox, rat gene coding for COX; COX Via-L, liver-type isoform of COX; COXVIa-L, COX Via-L;
COX Via-M, COX
mtDNA,
mitochondrial
reaction;
pfu, plaque-forming unit(
muscle-type
M Na,.citrate
isoform of COX;
kb, kilobase
DNA; nt, nucleotide(s);
ends; RT, reverse transcriptase; M NaCI/O.OlS
Via-M;
or 1000 bp;
PCR, polymerase
RACE, rapid amplification SDS, sodium dodecyl pH 7.6.
chain
of cDNA
sulfate; SSC, 0.15
308 HL: HM: BM: HL:
‘(I
HM: A'XSGCT TTGCCT Cl-G AGGCCC CTGACC CGGGGC TTGGCC EM: AM ............ .A. T .. T .. .GT .............. FZ.l: CCTCTPAAGCPCCTCAGTCGGAG-A% ...... RL: G T.G BL: --- T.G HL: -__ ___ ___ ___ -_- -__ ___ ___ --- --- --- AlU T.G KM: EM: RM: FL: BL: HL:
GGAGGAGCA GGAGCT CGT ... ... A ....... . ,.C ..... . ........ . AAC ... --- --- TC. ...... ... --- --- TC. ..... . ... --- --- TC. ..... .
HM: EN: RM: RL: BL: HL:
GCC CTC TGC ACC ............ ,.T ...... T.G .GA G.G A .. .TG .GA G.G A .. .TG ... G .. A .. .TG
HM: BM: PM: RL: BL: HL:
TTC ... ... ... ... ...
HM: BM: RM: RL: BL: HL:
CAC ACT CTG ...... T.T ..... . ... ... ... ... ... ... ... ... ..... .
CGT AK ATC GTC GTG ATC
ACC TGGCGT ........ . ... ..... . .lT ... AAG .TG ... AAG .TG ... AAG
CCC TAC CAA ... ..... . ..... . ... G ..... .CC G .... . .CC G ..... .CC
CRC ... ... G.G G.G G.G
(36) (79) (50) 1251
(24) 1117) (1561 1139) (110) (79) 178) (1711
CTC CAC TCG GGC CAC ............... A.G ... G.T ...... ... A.G ... CGA ... A.G A.G ... CA. ... ... A.G ... CA. ...
------GAA GGA GGA
------GAG GAG GAG
CCG GA. GA. GA. GA. GA.
CCC CCC GAG ..... . .CA ..... . ... A.A ...... A.A ...... A.A ......
(210) 1193) (1641 (139) (133) (231)
CAC CTC CGC ATC CGC ACC AAG CCC ........ . ............... .............. . ......... ... ......... A.G ... ...... ... ......... A.G T ........ ... ......... A.G ........ .
TAC .T. .T. .T. .TT .TT
CCC TGG GGG T.A ..... . T .......... ........ . ........ . ........ .
GAC GGC AAC ......... . ... ... ... ... ... ... ... ... ,.T ... ...
(270) (253) (224) (199) (1961 (291)
TI'CCAC AAT ......... ......... ......... ..... . ... ..... . ...
AGC CC. CC. CCT CCT CCT
TAT .GG .GG .TC .TC ...
CTG ACC 'IX ..... . ... ........ . ...C ... .A. ... ..... . ... ......
GGC .A. .A. .AA .AA .AA
GTG CTG GCG CTG CCC AGC GTG .G. ........ . ... ...... ........ . ... ........ . T.C G ........... G.G ... T.C G ....... . ... G.G ... T.C G.C ..... . ... G.G ...
TTC AAC TCC C ........ C.T ... .G. C ..... GTT C.G ... GT. C.G ... GTG
CTG T.C ... GCC GCC ACT
AGC GCY GCC AAAQZA . ... ..... . ... ..AT ........ ... .GC ... C.C ... ... .GC ... C.C ... ... .W ... C.T ...
CGC ... .AT .A. GAG .A.
CAC GTG AAC CCT CTG CCC ACG GGC TAC GAA .GG ... ........................ ..... . ... ... T ....... . ........ . ... A ....... . ... ... ... ..... . ... ... ........ . ... ... ... ..... . ... ... ..... . ... ... ... ... .........
CAC A.G ... G.T G.T G.T
CCC ... ... GAG GAG GAA
n;vr 1330) 'IX%, (3131 TOA (284) TAA (2591 TM (2581 TM (351) (352) (338) 13091 1337) (427)
Fig. 1. Alignment
HM: BM: RM: RL: HL:
(352) (338) (348) (337) (427)
HM: BM: RM: RL: HL:
(371) (3461 (394) (438) (5431
of the nt sequence
(5’ - 3’ in the mRNA
sense) of the human
muscle (HM) cDNA
from pHCOX6aM
with those from bovine mus-
cle (BM; Smith et al., 19911, rat muscle (RM; Schlerf et al., 1988), rat liver (RL; Schlerf et al., 1988), bovine liver (BL; Ewart et al., 1991) and human liver (HL, Fabrizi
et al., 1989) coxVla
mize identity. The presumed by the black arrowhead. in the importation cDNA
isoform
start codons,
cDNAs.
Dots in coding
stop eodons and polyadenylation
The first 26 nt in the rat CoxVla-M 11, extending
nt identical
to the HM sequence;
signals are in bold. The presumed COXVIu-M
from nt 103 to a poly(A) tail) was isolated
dashes
site ofcleavage
(italics), deemed to be the 5’-untranslated
coding region as shown (see section a). The human
presequence
(insert of pCOX6a.
sequences
region denote
were inserted
of the presequences
region by Schlerfet
al. (1988), are aligned
cDNA was isolated as follows: A partial-lengrh
from a human
to maxiis denoted
adult skeletal muscle AgtlO cDNA
COXVIu-M
library using the
EcoRI insert of the liver-specific COXKa-L cDNA from pCOX6a.24 (Fabrizi et al., 1989) as a probe at low stringency. Prehybridization and hybridization were performed at 42°C overnight, as described (Zeviani et al., 1987); filters were washed at 50°C in 2 x SSC and 0.1% SDS, and then in 0.5 x SSC and 0.1% SDS, and exposed to Kodak XAR-5 X-ray film with an intensifying screen (DuPont Cronex) at -70°C. Using the EcoRl insert of pCOX6a.11 clone (ZHCOX6a. 1) with a COXVIa-M insert startas a probe of a AZAP II rM library of human adult heart cDNA, we isolated a longer partial-length ing at nt 39. To isolate sequences muscle mRNA cDNA
(cDNA
synthesis;
upstream
from nt 39, we used RT-RACE:
CyclerM Kit, Invitrogen),
the cDNA
was then tailed with poly(A)
coxVla-M was amplified by RACE (Frohman, primer. Finally, a f~l-lent coxVZ&%4 cDNA into a pCRM
1000 vector (Invitrogen)
has been deposited
in GenBank
under
first strand cDNA was synthesized
using an oligo(dT) oligodeoxynucleotide using dATP
in the presence
by performing
RT-PCR
(5’-GACTCGAGTCGACATCGA[T],,) of terminal
deoxynucleotidyl
transferase,
on human
skeletal
to prime first-strand and the 5’ region of
1990) using the oIigo(dT) primer as the sense primer and the complement to nt 279-304 as the antisense was synthesized by RT-PCR using forward (nt 1-21) and reverse (nt 371-350) primers; it was subcloned
to create clone pHCOX6aM, accession
No. M83308.
and sequenced
on both strands
(Sanger
et al., 1977). The human coxYI&M
cDNA
309 (Fig. 2) of this cDNA, we conclude that it encodes the precursor to the muscle-specific isoform of human COX Via. The mature pol~eptide coding regions of the L- and M-type isoform genes are much more similar between species than are either the L- or M-types within species (Fig. 2B). The human L and M coding regions share only 62% aa identity, similar to the divergence of the rat and cow L and M isoforms (58% and 59%, respectively). On the other hand, the human muscle isoform mature polypeptide shares a higher degree of identity with the analogous bovine and rat muscle isoforms (81% and SO%, respectively), as does the human liver isoform with the analogous bovine and rat isoforms (88%). These data imply that the tissue-speci~c COX Via subunit genes most likely arose via a gene duplication event which occurred prior to the divergence of these species, and probably prior to the mammalian radiation. Despite the approx. 407; difference in the primary structure of the two COX Via isoform polypeptides, the secondary structures of human COX Via-L and Via-M are remarkably conserved, as reflected by their hydropathy profiles; the similarity between corresponding tissue-specific isoforms of human and rat is even more striking (not shown). The lengths of the human COXVZu-L and COXVZu-A4 3’-untranslated regions are also quite different. This region in the M-type isoform is only 41 nt long (similar to the 33 nt 3’-untranslated region found in bovine COXVZPM), but is 192 nt in the L isoform, The same pattern holds in the rat Cox VZu isoform genes: 110 nt for the M isoform as compared to 179 nt for the L isoform. We note that the 3’-untranslated region of the muscle isoform of another housekeeping gene, phosphoglycerate mutase, is also significantly shorter than that of the analogous nonmuscle
1982; Kuhn-Nentwig and Kadenbach, 1985; Kadenbach, 1986; Biige and Kadenbach, 1986). In mammals, COX subunits Via, VIIa, and VIII appear to be present in difFerem isoforms in heart and muscle as compared to liver and other tissues, as suggested by the different electrophoretic profiles of the enzyme in rat, chicken and cow (Merle and Kadenbach, 1980; Kadenbath et al., 1983a; Takamiya et al., 1986; Sinjorgo et al., 1987; Capaldi et al., 1988; Yanamura et al., 1988; Cao et al., 1988), and by the partial amino acid sequences of the subunits from beefheart and liver (Kadenbach et al., 1983b; Capaldi et al., 1988; Yanamura et al., 1988). The existence of two different isoforms of subunit Via has been confirmed by the isolation of two different but related cDNAs encoding this pol~eptide in heart and liver from rat (Schlerf et al., 1988) and cow (Smith et al., 1991; Ewart et al., 1991). Similarly, pairs of COX isoform cDNAs encoding bovine COX VIIa (Seeian et al., 1989; Seelan and Grossman, 1991; 1992) and VIII (Lightowlers et al., 1990) have now been isolated. We previously isolated a full-length cDNA specifying the liver-type isoform of human COX Via (i.e., COXP’Zu-L; Fabrizi et al., 1989). We now report the isolation of a fulllength cDNA specifying the muscle-type isoform (i.e., CctxVZu-&Q, and present a transcriptional analysis of both isogenes. EXPERIMENTAL
AND
DISCUSSION
(a) Isolation and analysis of human CUXVIa
cDNAs
Using the procedures described in the legend to Fig. 1, we isolated a full-length cDNA specifying COX Via-M (i.e., insert of clone pCOX6aM). Based on alignments of the nt sequence (Fig. 1) and the deduced aa sequence
BM: malplkslsrgl ASAAKGDHGGTGARTWRFLTFGLALPSVALCTLNSWLHS--GHRERPAFfPYHHLRIRTKPFSWGDGNHTFFHNPRVNPLPTGYEKP RM:[---plrvlsrxm]ASASKGDHGGAGANTWRLLTFVLALPSVALCS~C~A--GHHERPEFIPYHHLRIRTKPFSWGDGNHTLFHNPHVNPLPTGYEQP HM: malplrplsrgl ASAAKGGHGGAG~~LTFVLALPSVALCTFNSYLHS--GHRPRPEFRPYQHLRIRTXPYPWGW;NHTLFHNSHVNPLPTGYEHP HL: SSGAHG~EG--SARMWKTLTFFVALPGVAVSMLR~LKSHHGEHERPEFIAYPHLRIRTXPFPWGDGNHTLFHNeHVNPLPTCYEDE BL: SSGAHGEEG--SARMWKA LTLFVRLPGVGVSMLNVFMXSHHGEEERPEFVAYPHLRIRSKPFPWG~~TLFHNPHVNGYEDE RL: SSGAHGEEG--SARIWKALTYFVALPGV~SMLNVFLKSRHEEHERPEFV * * * * * **** ** * * ***** ** ******* *** ********
8. Pwcentage
BM RM HM HL BL RL Fig.2. Theaa
i%EMH& -82
awyuence
81 80 --
identities
UBLBba 62 59 64 62 62 58 -88 --
(mature polypeptide)
59 58 59 88 91 __
alignmentsand sequenceidentities. (A)Alignmentofthededuced COX
are in lower case; mature
polypeptides
are in upper case. The presumed
presequence
VIasubunitpolypeptides.Nomenclatureasin Fig. l.Presequences of rat COX Via-M
is in brackets
(see section a);the x at position
-2 denotes an ambiguous codon (AGX) encoding either Ser or Arg. Dots are spaced at lo-aa intervals. Asterisks below the aligned aa sequences denote conserved aa. (B) Sequence identities (% identical aa) of mature COX Via among human, rat, and bovine, based on the aa-alignment shown in A (seeFig. 1 legend).
310 isoform (37 vs. 913 nt; Sakoda et al., 1988). The functional significance of these 3’untranslated regions is unknown. Like bovine COXVIa-M, human COXVIa-M encodes a presequence for importation into mitochondria. Although most nuclear-encoded polypeptides which are imported into mitochon~a contain a cleavable presequence at the N terminus (Roise and Schatz, 1988; Hendrick et al., 1989), neither the rat CoxVZa-M (Schlerf et al., 1988) nor the human COXVZa-L (Fabrizi et al., 1989) cDNAs appear to encode a presequence. However, upon closer inspection of the published rat CoxYla sequences (Schlerf et al., 1988), we believe that rat CoxVZa-M does indeed encode a prequence which may have been overlooked inadvertently. The published rat CoxVIa-M sequence is, in retrospect, most likely partial length, beginning at the 5’ end at deduced presequence codon No. 3 (i.e., Pro). We believe that the first ATG triplet in the published rat CoxVIa-M sequence (at nt positions 24-26 in Fig. 1) does not encode the initiator Met, but rather, encodes the last aa (i.e., Met 1) of the COX Via-M presequence. This view is supported by the observation that alignment of the rat 23-nt region immediately prior to this Met codon [considered by Schlerf et al. (1988) to be the 5’-untranslated region] with the analogous regions in the human and bovine COXVIa-M presequences shows a very high conservation of nt sequence among all three genes (see Fig. 1). Moreover, if one allows for a 1-nt insertion between nt positions 23 and 24, the 27 nt preceding the coding region for the mature polypeptide would encode a 9-aa peptide (bracketed region in Fig. 2A) with striking aa identity to the last 9 aa of both the human and bovine deduced presequences.
Fig. 3. Northern
blot hybridization.
et al., 1977) from human
psoas
Total RNA (25 pg) isolated (Ullrich
muscle
(HM),
heart (HI-L), liver (HL),
brain (HB) and monkey kidney (MK) were separated by electrophoresis through a 1% agarose - 2.2 M fo~aldehyde gel (Lehrach et al., 1977). transferred
to a nylon membrane
10 x SSC, irradiated of 30 cm), hybridized labeled
(Feinberg
pCOX6a.24,
(GeneScreen,
(Church and
and subjected
ping off the hybridizing
and Gilbert,
Vogelstein,
1983)
Nuclear)
in
signaL in 50:;
from pCOX6a.
1984) with random-primer COXVIa-L
to autoradiography
It (left panel).
cDNA
from
(right panel). After strip-
formamide
buffer at 65°C for 1 h, the filter was reprobed cDNA
New England
with UV light for 10 min (260 nm lamp at a height
and 10 mM phosphate with Labeled COXWu-M
Each probe was labeled to a spe-
cific activity of about 1 x 10s cpmjmg, and 5 x lo6 cpm/ml was used in each hybridization. Arrows indicate the 28s and 18s rRNAs. COXVlaM mRNA, migrating
at about 450 nt, is recognized
heart only; COXVla-L
mRNA,
migrating
in skeletal muscle and
at about 620 nt, is transcribed
in all tissues examined.
mined with human COXVZZa-L and COXVZIa-M (Arnaudo et al., 1992), the only other human COX subunit known to have tissue-specific isoforms (see Rizzuto et al., 1989).
(b) Transcriptional analysis of COXVIa We performed Northern analysis of total RNA extracted from human adult skeletal muscle, heart, liver and brain, and from monkey (Macaca fascicularis) kidney, using the human COXVZa-L and COXVZa-M cDNAs as hybridization probes (Fig. 3). The filter was first hybridized with the liver-type cDNA, giving a hybridization signal of about 620 nt in all lanes. After stripping the signal off the filter, it was rehybridized with the muscle-type cDNA, giving a signal at approx. 450 nt in just the lanes containing human skeletal muscle and heart RNA. Most of the difference in the sizes of the ‘liver-specific and ‘muscle-specific’ hybridizing bands, about 170 nt, can be ascribed to the 151-nt difference in the sizes of the 3’-untranslated regions of the two cDNAs. The pattern of transcription in primate tissues is similar to that found in rat (Schlerf et al., 1988): the muscle isoform is transcribed in a tissue-specific manner (i.e., only in muscle and heart), whereas the liver isoform is expressed ubiquitously (i.e., not only in liver, kidney and brain, but in muscle and heart as well). Similar results have been ob-
(c) Clinical implications The isolation of cDNA clones for the putative isogenes of the human COX nuclear-encoded subunits is particularly important for the definition of the molecular basis of Mendeli~-inhe~ted COX deficiencies. These are often expressed in a tissue-specific manner, with myopathy as the predominant or exclusive manifestation (Bresolin et al., 1985; DiMauro et al., 1985; 1988; Takamiya et al., 1986; Schon et al., 1988; Nonaka et al., 1989). The study of the regulation of expression of the isogenes of human COX subunits should help us investigate the molecular basis of the tissue-specific human COX deficiency diseases. In some cases the infantile myopathies associated with COX deficiency are reversible, with the reappearance of normal COX activity in muscle at about l-2 years of age (DiMauro et al., 1985). The existence of devefopment~ly-re~lated~ nuclear-encoded COX subunits has been suggested (Kuhn-Nentwig and Kadenbach, 1985). Mutations in putative fetal or neonatal COX isozymes could be a cause of these so-called ‘benign’ or ‘reversible’
311 infantile
myopathies,
since the biochemical
defect would
correct itself when the putative adult isoform began to be expressed (Schon et al., 1988). This hypothesis is consistent with the fact that we were unable to isolate a COX Via M-type isoform cDNA from either a human fetal muscle or a human myotube cDNA library when the ‘adult’ VIaM cDNA was used as a probe. The occurrence of two different isoforms of subunit Via in muscle and heart raises the possibility that there is developmental switching of these subunits as well, similar to the switching of COX Via isoform expression in skeletal muscle during bovine development (Ewart et al., 1991). Thus, the availability of a pair of human COX subunit Via isoform genes should be useful not only in further investigations into the coordinate regulation of isoform biosynthesis, but also in the analysis of the tissue-specific COX deficiencies.
DiMauro,
S., Bonilla, E., Zeviani,
Mitochondrial DiMauro,
myopathies.
S., Zeviani,
E., Miranda,
M., Rizzuto,
A. and Schon,
c oxidase in mitochondrial 353-364. Ewart, G.D.,
Zhang,
cytochrome G.M.,
Schon,
Y.-Z.
cytochrome
Switching
of bovine
Capaldi,
R.A.:
in skeletal muscle during
H., Mita, S., Kadenbach, specifying
B. and
subunit Via of human
Nucleic Acids Res. 17 (1989) 6409. B.: A technique
fragments
M.A.:
M.A.,
RACE:
Gelfand,
Protocols: Hendrick,
rapid
D.H.,
for radiolabeling
DNA re-
to high specific activity.
Anal. Bio-
amplification
Sninsky,
J.J.
A Guide To Methods
J.P., Hodges,
proteolytic peptides
cleaved
by two matrix
PCR
1990, pp. 28-38.
L.E.: Survey of N-terminal precursor
proteases
share
proteins:
leader
a three-aminoacid
Sci. USA 86 (1989) 4056-4060.
J., Hartmann,
cytochrome
dodecylsulfate-gel
ends. In: Innis,
And Applications.
sites in mitochondrial
B., Jarausch,
mammalian
of cDNA
and White, T.J. (Eds.),
P.E. and Rosenberg,
cleavage
motif. Proc. Natl. Acad.
We thank Drs. F.S. Walsh and L. Leinwand for kindly providing the human muscle and myotube cDNA libraries, respectively, and J. Rogers for expert technical assistance. This work was supported by grants from the National Institutes of Health (NS28828, NS 11766, and AG08702), the Muscular Dystrophy Association, the Aaron Diamond Foundation, and Graziella and Libero Danesi, Milano, Italy. S.M., Y.K. and R.R. were Fellows of the Muscular Dystrophy Association. Y.K. is the David Warfield Fellow in Ophthalmology of the New York Community Trust and the New York Academy of Medicine.
and
132 (1983) 6-13.
Frohman,
Kadenbach,
ACKNOWLEDGEMENTS
20 (1988)
of a cDNA
endonuclease
them.
Biomembr.
R., Nakase,
c oxidase.
H., Bonilla,
defects in cytochrome
disease. J. Bioenerg.
Lett. 292 (1991) 79-84.
A. and Vogelstein,
striction
A., Nakase,
FEBS
E.A.: Sequence
Feinberg,
R., Lombes,
E.A.: Molecular
subunit Via isoforms
Rizzuto,
M. and DeVivo, D.C.:
17 (1985) 521-538.
c oxidase
development. Fabrizi,
M., Nakagawa,
Ann. Neurol.
R. and Merle, P.: Separation
c oxidase
into 13 polypeptides
electrophoretic
procedure.
Anal.
of
by a sodium Biochem.
129
(1983a) 517-521. Kadenbach,
B., Ungibauer,
L.: The complexity
M., Jarausch,
of respiratory
J., Buge, U. and Kuhn-Nentwig,
complexes.
Trends
Biochem.
Sci. 8
(1983b) 398-400. Kadenbach,
B.: Regulation
organisms. Kuhn-Nentwig, chrome
of respiration
J. Bioenerg.
Biomembr.
L. and Kadenbach,
c oxidase
and ATP synthesis
in higher
18 (1986) 39-54.
B.: Isolation
and properties
from rat liver and quantification
of cyto-
of immunological
differences between isoenzymes from various rat tissues with subunitspecific antisera. Eur. J. Biochem. 149 (1985) 147-158. Lehrach,
H., Diamond,
D., Wozney,
J.M. and Boedtker,
lecular weight determinations by gel electrophoresis conditions: a critical reexamination. Biochemistry
H.: RNA mo-
under denaturing 16 (1977) 4743-
4751. Lightowlers, REFERENCES
Capaldi.
R., Ewart, G., Aggeler, R.A.: Isolation
ing two isoforms Arnaudo,
E., Hirano,
M., Seelan,
Fabrizi, G.M., Grossman, specific expression
R.S.,
Milatovich,
L.I., Francke,
and chromosome
N., Zeviani,
M., Bonilla,
ske, S., Nakagawa,
oxidase from bovine 383-390. Cao, X., Hengst,
c oxidase.
S.: Fatal infantile cytochrome detectable
B.: Influence of buffer composition, membrane and the kinetics of reconstituted cytochrome-c liver and heart.
Eur. J. Biochem.
and tissue-specificity erg. Biomembr.
161 (1986)
M., Mengel, T. and Kadenbach,
D.G., Zhang,
Y. and Yanamura,
of the mitochondrial
respiratory
cytochrome
sequencing.
encod-
C,,
B.: On the heterogeneity
cytochrome
c oxidase.
of vertebrate
B.: Kinetic and structural
differences
J.
cyto-
Hoppe-Seyler’s
Z.
between
c oxidase from beef liver and heart. Eur. J. Biochem.
125
(1982)239-244. Nonaka, I., Koga, Y., Ohtaki, E. and Yamamoto, M.: Tissue specificity in cytochrome c oxidase deficient myopathy. J. Neurol. Sci. 92 (1989) 193-203. Rizzuto, R., Nakase,
H., Darras,
T., Walsh, F., Kadenbach, subunit
to chromosome
B., Francke, B., DiMauro,
VIII of human
U., Fabrizi, G.M., Mengel, S. and Schon, E.A.: A gene
cytochrome
11 and is expressed
c oxidase
is localized
in both muscle and nonmuscle
tissues. J. Biol. Chem. 264 (1989) 10595-10600. S.: Mitochondrial
W.: Complexity chain. J. Bioen-
Sakoda,
S., DiMauro,
Proc. Natl. Acad. Sci.
of bovine cytochrome 1.
chrome c oxidase polypeptide chain composition. Physiol. Chem. 361 (1980) 1257-1259.
Roise, D. and Schatz, (1988) 4509-4511.
20 (1988) 291-311.
Church, G. and Gilbert, W.: Genomic USA 81 (1984) 1991-1995.
L. and
of the cDNAs
of subunit
Merle, P. and Kadenbach,
specifying
L., Schlerf, A., Droste,
R.A., Halphen,
enzyme
Y.Z., Calavetta,
Biol. Chem. 265 (1990) 2677-268
Merle, P. and Kadenbach,
B.: Complexity of nuclear-encoded genes of mammalian c oxidase. Ann. NY Acad. Sci. 550 (1988) 337-347. Capaldi,
Gene
Leech, R.W., Shan-
c oxidase deficiency: decrease of immunologically in muscle. Neurology 35 (1985) 802-812. Bttge, U. and Kadenbach, lipids and proteases,
of genes specifying
cytochrome
E., Miller, R.H.,
M. and DiMauro,
C.-L.,
U. and Schon, E.A.: Tissue-
assignment
two isoforms of subunit VIIa of human 119 (1992) 299-305. Bresohn,
A., Hsieh,
R., Zhang,
and characterization
S., Shanske,
presequences. S. and Schon,
J. Biol. Chem. 263 E.A.: Isolation
cDNA encoding the B isozyme of human phosphoglycerate (PGAM) and characterization of the PGAM gene family. Chem. 263 (1988) 16899-16905.
of a
mutase J. Biol.
312 Sanger, F., Nicklen, terminating
S. and Coulson,
inhibitors.
A.R.: DNA sequencing
Proc. Natl. Acad.
with chain-
Sci. USA 74 (1977) 5463-
5467. Schlerf, A., Droste,
M., Winter, M. and Kadenbach,
of two different genes (cDNA)
for cytochrome
from heart and liver of the rat. EMBO Schon, E.A., Bonilla, E., Lombes, cytochrome
oxidase
c oxidase
subunit Via
C.T., Nakase,
H., Rizzuto,
S.: Clinical and biochemical
deficiencies.
Ann.
NY Acad.
studies on
Sci. 550 (1988)
348-359.
Nucleic Seelan,
of a cDNA
D., Lomax, M.I. and Grossman, for bovine cytochrome
L.I.: Nucleotide
c oxidase
subunit VIIa.
R.S. and Grossman, Characterization
L.I.: Cytochrome and expression
c oxidase
subunit
of bovine cDNAs.
VIIa
J. Biol.
Seelan, R.S. and Grossman,
L.I.: Structure
isofoorm gene for bovine cytochrome
and organization
of the heart
c oxidase subunit VIIa. Biochem-
Via encodes
Takamiya,
K.M.C.,
Hakvoort,
and Muijsers,
T.B.M.,
A.O.: Human
Durak, cytochrome
I., Draijer,
J.W.,
B&him.
Grossman, L.I. and Lomax, isoform of bovine cytochrome
a presequence.
S., Yanamura,
Biochim.
Post,
c oxidase isoenzymes
W., Capaldi,
Sengers, R.C.A., Trijbels, J.M.F. myopathies
involving
M.I.: The c oxidase
Biophys.
Acta
1089
R.A., Kennaway, and Ruitenbeek,
the respiratory
chain:
N.G., Bart, R.,
W.: Mitochondrial
a biochemical
analysis.
Sci. 488 (1986) 33-43.
Ullrich, A., Shine, J., Chirgwin, J., Pictet, R., Tischer, E., Rutter, W.J. and Goodman,
H.M.:
Yanamura,
Zeviani,
Rat insulin genes: construction sequences.
Science
W., Zhang,
Y.Z., Takamiya,
differences
between
specific
M., Nakagawa,
Sherbany, c oxidase.
heart
of plasmids
con-
196 (1977) 1313-1318. S. and Capaldi,
R.A.: Tissue-
and liver cytochrome
c oxidase.
27 (1988) 4909-4914. M., Herbert,
A.A., Miranda,
lation of a cDNA
istry 31 (1992) 4693-4703. J.K.P.
subunit
Biochemistry
Chem. 266 (1991) 19752-19757.
Sinjorgo,
Smith, E.O., BeMent, D.M., cDNA for the heart/muscle
taining the coding
Acids Res. 17 (1989) 6410.
isoforms.
and properties.
Acta 850 (1987) 144-150.
Ann. NY Acad.
Seelan, R.S., Scheuner, sequence
Biophys.
(1991) 266-268.
J. 7 (1988) 2387-2391.
A., Moraes,
R., Zeviani, M. and DiMauro,
B.: Characterization
from heart and skeletal muscle: purification
J., Lomax,
A.F., Dimauro,
clone encoding
Gene 55 (1987) 205-217.
subunit
M.I., Grossman,
S. and Schon, IV of human
L.I.,
E.A.: Isocytochrome