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7
mtDNA copy number [x10 ]
5
7
4
3
2
1
4
3
2
1
H
G
F
E
D
0
C
A
0
B
mtDNA copy number [x10 ]
(K):FGPELD9<I@ED8KLI<Q<9I8=@J?FF:PK<J
Female ID
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Z DK):FGPELD9<IG<ILE@KF=MFCLD<
J<<DJ<HL8C8:IFJJJG<:@<J
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Absolute mtDNA
7
copy number [x10 ]
Relative copy number
10
0.8
***
0.6
***
0.4
**
0.2
1
0.1
0.01
0.001
0.0001
1
ce
ll
2
ce
ll
4
ce
ll
8
ce
16 l l
ce
32 ll
ce
64 ll
c
12 ell
8
c
25 ell
6
ce
ll
0.0
l
el 1k gh ng re ly ly ld ly ud ite ite ite ite ite ite ite -5 22
-c hi lo he iboibohieibo b momomomomomom rimim2
ob sp ep ep s ep -so-s -s -s -s -s -s p pr
51
8 10 13 17 20 22 26
% % %
30-50 -90
/
e 0 60
m 4
do
No mtDNA replication until epiboly and early somitogenesis
Epiboly phase has similarities with implantation
$JFC8K@FEF=+"JEFE+"J=IFDQ<9I8=@J?
<D9IPFJN@K?!.JFIK@E>
8 hpf
24 hpf
48 hpf
Log
absolute
copy
number
#@>?M8I@8K@FE@E8CCJK8><JF=;<M<CFGD<EK
72 hpf
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•
•
•
•
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8C:LC8K<; 9FKKC<E<:BJ@Q< 98J<;FEG<I:<EK8><;< EFMF DLK8K@FE KF
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•
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•
•
<EFMFDLK8K@FEJF::LI8KI8E;FDEFEG8K?F><E@:8E;G8K?F><E@:
$=G8K?F><E@:DLK8K@FEJ<O:<<;<OGI<JJ@FEK?I<J?FC; → ;<EFMF;@J<8J<
-<GC@:8K@FE<IIFIJ+FCPD<I8J<"8DD8I<GC@:8K<JDK)DFJKC@B<CP:8LJ<
L<KFK?<?@>?@EKI8@E;@M@;L8CM8I@8K@FE<M<IP=<D8C< J<<DJ8KI@JB
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(LK8K@FE CF8; ;@JKI@9LK@FE @E+" FF:PK<J
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100
Heteroplasmy (%)
80
60
40
20
0
m
A
43
2
.3
>G
#1
m
3
24
3
.
A
>G
#2
m
3
24
3
.
A
>G
#3
m
3
24
3
.
A
>G
#4
m
A
43
2
.3
>G
#5
>C
>G
T
T
7
3
48
99
.8
14
.
m
m
FKKC<E<:BJ@Q<J=FID
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1
D
"
D
"
D
"
D
"
D
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D
/"
D
/
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$
67
67
67
67
67
67
67
FKKC<E<:B J@Q<J :8C:LC8K<; FE K?< 8JJLDGK@FE F= ><E<K@: ;I@=K FECP
(LK8K@FE CF8; ;@JKI@9LK@FE @E+" FF:PK<J
QP>FK<J 8E;9C8JKFD<I<J
100
)FDLK8K@FECF8;
Heteroplasmy (%)
80
.B<N<;
60
40
20
0
m
A
43
2
.3
>G
#1
m
3
24
3
.
A
>G
#2
m
3
24
3
.
A
>G
#3
m
3
24
3
.
A
>G
#4
m
A
43
2
.3
>G
#5
>C
>G
T
T
7
3
48
99
.8
14
.
m
m
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0
0 .<C<:K@FE*3+#*.
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Only 20-30% of OXPHOS capacity required for embryogenesis
Normally 200,000 copies mtDNA → 50,000 copies will be enough (fully functional)
Reserve capacity reflected in mtDNA copy number
Patients develop severe disease during life (less reserve capacity)
I@K@:8CK?I<J?FC;F=DK):FGPELD9<I;LI@E>
DFLJ<<D9IPF><E<J@J
Timothy Wai et al. Biol Reprod 2010;83:52-62
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Collaborators and Support
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