THE ENZYMIC AND MORPHOLOGIC ORGANIZATION
OF THE MITOCHONDRIA
Albert
Department
of Physiological
Chemistry,
L. Lehninger
Johns Hopkins
I N THISPAPERI shall describe some of the
information we have recently obtained
regarding the enzymic and molecular or
ganization of the mitochondria,
which as
you know are very small particulate
or
ganelles in the cytoplasm of all aerobic
cells. These bodies have been found to cata
lyze one of the most fundamental
activities
of the cell, namely, the transformation
of
the energy yielded by oxidation of food
stuffs into the so-called phosphate-bond
en
ergy of adenosine triphosphate.
This proc
ess of respiration
and phosphorylation
is
extremely complex and involves the inter
action of at least seventy different enzymes
and coenzymes in an integrated fashion.
The mitochondria
have a characteristic
ultrastructure
in which these enzymes are
embedded,
and it is now possible to con
sider in some detail the intramitochondrial
location and function of these important
energy-transforming
molecules.
First, let us consider the organization of
oxidative metabolism in purely biochemical
terms. Figure 1 shows the usual text-book
representation
of the final common pathway
of biologic oxidation in animal tissues. You
will recall that all three of the major food
stuffs of the cell (carbohydrate,
fat and
protein) ultimately are degraded in the tis
sues to a two-carbon unit, namely, acetyl
coenzyme A. The acetate group then un
dergoes oxidation by the Krebs citric acid
cycle, and in this process the two carbon
atoms of acetate become oxidized to car
bon dioxide. The oxidation of acetate is
finally completed when pairs of hydrogen
atoms are removed from certain of the in
termediates of the Krebs cycle by dehydro
genases. These hydrogen atoms, or their
equivalent in electrons, pass along the respi
University
School
of Medicine
ratory chain via the cytochromes until they
meet molecular oxygen and reduce it to
form water.
The oxidation of these foodstuffs releases
large amounts of energy. But this energy is
not released simply as heat. In the cell the
energy of biologic oxidation is largely re
covered as chemical energy, as the so-called
phosphate-bond
energy of adenosine
tri
phosphate (ATP).
Several years ago we were able to prove
that the site of this conversion of oxidative
energy into ATP energy is the respiratory
chain. Figure 2 shows this chain in more de
tail, and you can see that electrons pass
from substrate to oxygen via a series of elec
tron carriers, including pyridine nucleotide,
a flavoprotein, and the four cytochromes.
Along this chain there are three energy
transforming mechanisms which use the en
ergy lost when a pair of electrons passes
from a specific carrier to the next to cause
the formation of ATP from adenosine di
phosphate
(ADP) and phosphate.
ATP is
thus the charged form of the energy carry
ing system and it is charged at the expense
of the energy lost during electron transport.
The enzymic mechanism of this energy
conversion is one of the great unsolved mys
teries of contemporary
biochemistry.
How
ever, Figure 3 provides a picture of what we
believe to be the probable form, in princi
ple, of the energy-coupling
mechanisms in
the respiratory
chain. I will not discuss
these principles and mechanisms in detail;
I want merely to impress you with the great
complexity of the energy-coupled
respira
tory chain. It consists of a series of cycles,
and cycles within cycles.
Some 10 years ago Kennedy and I dis
covered that the entire Krebs cycle complex
Presented at the IX International Congress of Pediatrics, Montreal, Canada, July 20, 1959.
ADDRESS:Baltimore 5, Maryland.
PEDIATRICS,
466
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September
1960
SPECIAL ARTICLES
467
the cell. Since then it has been found that
the mitochondnia
of all cell types which
have been examined, whether animal or
of enzymes, together with the respiratory
chain and these energy-transforming
mech
anisms, are located in the mitochondria
of
CITRATE
4'
[GLUCOSE I
CIS —¿ACONITATE
.4'
ISO-CITRATE
CYTOCHROME
4,
OXALOSUCCINATE
PYRUVATE
‘¿
SYSTEM
\
@-KETOGLUTARATE ÷
FATTY
ACIDS
—¿*1ACETYL—CoiJ
S@CCINATE +
+
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7
MALATE
[@@NO ACIDSJ
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4'
t
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OXALACE TAT E
L KREBS
TRICARBOXYLIC@LELECTRON
TRANSPORT]
ACID
CYCLE
Ftc.1.Krebstricarboxylic
acidcycle.
ATP
ATP
‘¿1'
@
1
Substrates—¿@DPN
I
equation:
DPNH
ADP+P
+ H@ + 3 P@ + 3ADP
Energy
liberated
Energy
recovered
by electron
as
Efficiency
Ftc. 2. Schematic
tive phosphorylation
1
c —¿@Cyta--@Cyta
—¿@
0
AD? +P
Overall
ATP
ATP
ADP+P
+ 0 —¿@DPN
transport
+ 3ATP
+ H20
= 55 KCAL.
= 36 KCAL.
= 65%
representation
mechanisms,
of electron transport and coupled oxida
showing the major energy relationships.
©
DP@@NH2-®
SUBSTRATES@'
DPN@ DPN-@-(X@
@ADP
AlP-F®
jADP
ATP
+
ATP+ ©
Ftc. 3. Schematicrepresentation
of probablereactionpatternof electrontransportand coupled
phosphorylation.
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THE
468
ENERGY-REQUIRING
,—<
@
FUNCTIONS
MOTILITY,
@—¿<
phate, which represents
the discharged
or
“¿spent―
form of the energy carrier system.
This, then, is the biochemical
picture.
OF CELL
CONTRACTION
BIOSYNTHESIS
OF
CELL
MATERIAL
@—¿<
@
ACTIVE
Now let us consider the ultrastructure
of
the mitochondria
as revealed by the elec
tron microscope. Figure 5 is a picture of rat
heart mitochondria
made by Palade. You
TRANSPORT
TRANSMISSION
OF
IMPULSES
BIOLUMINESCENCE
ADP +
SPENT FORMJ
ENERGY TRANSPORT
SYSTEM
IATP
[@@RGED FORM
02ff
cARBOHYDRATE
CO2
will see that the mitochondria
have an outer
double
membrane
and a number
of septa
running
across the mitochondrion,
termed
the cristae.
+ -420
I 111
microns
FUELS
E@L(;.4. The
EXHAUST
central
role
of mitochondria
drive
the
different
energy-requiring
Each mitochondrion
long
and
less than
Figure 6 shows diagrammatic
in energy
functions
of
the cell.
ing
system.
chondria
this enzymic
As
may
Figure
thus
energy-convert
4 shows,
be looked
the
upon
in
less periodically
mito
to from
as the
representa
tions of mitochondrial
structure.
At the top
is a longitudinal
section of a mitochondrion,
which shows an outer membrane
surround
ing it and an inner membrane
plant, contain
is about 3
a micron
thickness;there is some variationin shape.
conversion. It is seen that the AlP energy is used
to
CELL
invaginates
that more
the so-called cristae. Within
inner membrane
or
into the lumen
the
is a relatively structureless
power plants of the cell. They oxidize food
stuff molecules with molecular oxygen and
matrix. The lower half of the Figure shows
a three-dimensional
representation
of a mi
in so doing, the energy
tochondrion.
of oxidation is har
nessed to cause the coupled synthesis of
ATP from ADP and phosphate. The ATP
Figure 7 indicates the dimensions of the
mitochondrial
membranes as deduced from
becomes the energy donor for the energy
requiring functions of the cell as is shown;
chonciria,
and in the process
of energy
or
ATP is ultimately
split to ADP and phos
conversion
Ftc. 5. Electron
micrograph
the
electron micrographs.
whether
cells,
of rat-heart
tile
regardless
they
In all kinds of mito
of cell types
are
from
mitochondrial
mitochondria
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(Palade).
animal
of origin
or
membrane
plant
con
SPECIAL
469
ARTICLES
180A
Fic.
6. Three-dimensional
aspects
of mitochondrial
sistsof two layers about 60 Angstrom
units
(A) in thickness,
layer
of about
separated
by a light
60A. For comparison,
in the mid
dle of tile Figure, are shown some data on
molecular sizes: A typical protein molecule,
hemoglobin, has a length of about 63A and
a thickness
of 45A. Hemoglobin
has a mo
lecular weigiit of 68,000, which is in the mid
dle range of molecular weights of globular
structure
(after
Palade).
Proteills. A phospholipid
30A long.
These dimensions
chemical
membranes
analysis
shows
molecule
are significant
of
tile
they
are
*
IFA
o130A
IJL
SECTION OF
MITOCHONDRIAL
DOUBLE
MEMBR ANE
composed
largely
of phospholipo-protein,
having
about 65% protein and 35% phospholipid.
These proportions and the thickness of the
membranes as revealed by tile electron mi
PROTEIN
0
because
mitochondriai
MOLECULE
1@O
A
is about
PHO5PHO
LIPID
MOLECULE
POSSIBLE
MOLECULAR
CONFIGURATION
OF
MEMBRANES
F'tc.
7.Dimensionsofiiiitochondrial
ineiiibranes.
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THE CELL
470
croscope are consistent with a “¿sandwich―flavoproteins and the different cytochromes
construction,
in which the double mem
together with the coupling enzymes which
form ATP during electron transport)
are
branes consist of two monolayers of protein
molecules each perhaps 60A thick, sepa
associated with the membranes alone. Fur
rated by a double layer of oriented lipid
thermore, it appears most probable from
molecules of about 60A thickness.
other lines of evidence that the respiratory
chain enzymes are located specifically in
Now let us consider
the intramitochon
the inner mitochondrial
membrane
as
drial location of enzymes and enzyme sys
shown.
tems concerned
in respiration.
How can
Now let us consider
in more detail the
such information be arrived at? Isolated mi
structure and localization of the respiratory
tochondria can be disrupted either mechan
mem
ically (by sonic oscillation for example) or chain enzymes in the mitochondrial
by application of chemical agents (such as branes. One of the first questions is this:
Are the respiratory chains in intact mito
detergents). Then, by differential ultracen
chondria made up of a specific and constant
trifugation
of fragmented
mitochondria,
ratio of the different individual electron car
fractions corresponding
to the mitochon
rier molecules, suggesting a high degree of
drial membranes and the matrix may be iso
molecular
organization
and design; or, are
lated. Such fractions may then be subjected
there widely different molar ratios of the
to chemical analysis, as well as enzymic
separate electron carriers, suggesting a more
analysis.
random organization? We have determined
Figure 8 indicates the gross intramito
the relative molecular proportions
of the
chondrial localization of the respiratory en
flavoproteins and cytochromes in fragments
zymes. Most of the Krebs-cycle enzymes are
of the mitochondrial membranes by using a
located in the inner matrix of the mitochon
highly sensitive spectroscopic method, sim
drion in a soluble form. Similarly, enzymes
ilar to that first described by Britton Chance.
of the fatty acid-oxidation
cycle are also
We have found that, within experimental
located in the matrix of the mitochondrion.
It therefore appears that the first stages of error, the different electron carriers compris
ing the respiratory
chain occur in nearly
biologic oxidation of pyruvate and fatty
equimolar proportions in the mitochondrial
acids occur in the inner matrix of the mito
membranes.
This is highly suggestive evi
chondrion.
dence,
but
not
necessarily proof, that these
On the other hand, it is seen that the en
catalytically active protein molecules of the
zymes making up the respiratory
chains (the
MEMBRANES
MAIR:X
?:R:es CYCLE ENZYMES
.%CONITASE
\IAL:C DEHYDROGENASE
F LMAR ASE
:SOCITRIC DEHYD.
CONDENSING
ENZYME
pYRUVIC AND KETOGLUT.
DEHYD. ETC.
FATTY
ACID
CYCLE
CROTONASE
ACYL
DEHYD.
ETC.
ETC.
ENZYMES
RESPIRATORY
CHAIN ENZYMES
DPN(BOUND)
FLAVOPROTEIN
CYTOCHROME
C
CYTOCHROME C1
CYTOCHROME B
CYTOCHROME
A
CYTOCHROME
A3
SUCCINIC DEHYD.
CHOLINE DEHYD.
@-HYDROXYBUTYRATE
DEHYD.
PHOSPHORYLATING
ENZYMES
Fic. 8. Enzyme localization in mitochondrion.
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SPECIAL
ARTICLES
respiratory chain are grouped together geo
metrically in an ordered sequence, presum
ably to permit rapid and efficient passage of
electrons along the chain.
This
finding
now
permits
us
to define
what we term a “¿respiratory
assembly― (Fig.
9). Such an assembly consists of one mole
cule of each of the six electron-carrier
pro
teins, together with perhaps nine additional
enzyme molecules which are specifically
concerned with the formation of ATP at
each of the energy transformingsitesin the
respiratory chain. Thus the complete respi
ratory assembly is made up of perhaps 15
separate specific enzyme molecules. If each
has a molecular
sembly
would
weight of 100,000, the as
have a particle
weight
of
about 1,800,000. Such an assembly would
represent the basic molecular machine for
respiratory energy conversion.
The question now arises: How many of
these
respiratory
assemblies
are present
in
the membranes of a single mitochondnion?
The answer can be arrived at rather easily,
at least approximately. We know the dry
weight and proteincontentof the mitochon
drion, and from spectroscopic
e
—¿
c
0
and chemical
03
02
CHAIN
471
determination
of the carrier molecules, it
can be calculated that a single rat-liver mi
tochondrion contains perhaps 5,000 such as
semblies of electron carriers and a single
rat-heart mitrochondrion
con taitis perl@aps
as many
as 20,000.
Of course
weight
\\
\\
ATP
of the mitochondrial
with purely
stituted
tically
a structural
@
A TP +
@i@_)
ci@ii@@
MECHANOENZYME
ATP
+
A DP
PRINCIPLE
Ftc.9. Diagram of a respiratory
assembly.Each
circle
represents
an individual
addition to the respiratory
zontally
in the diagram,
enzyme
protein.
In
carriers arranged hori
there
are three
additional
enzymes at each of the three coupling sites in the
chain, which participate in the conversion of re
spiratoryenergy intoATP. It ispostulatedthatthe
enzyme molecules E, E', and E―are mechano
enzymes which may change their configuration de
pending
upon
whether
or not
phosphorylated
they
state.
are
in
the
membrane,
function,
of many different
or
active
protein
but is con
types of cataly
molecules
organized
geometrically to carry out electron transport
and oxidative phosphorylation.
In short, this
membrane is not a dead wall, but is a very
complex enzyme system.
Another approach has permitted
us to
make some deductions about the disposition
of these respiratory-carrier
assemblies in the
membranes of the mitochondnion. We have
subjected the mitochondnial membranes to
sonic oscillation, which shatters the mem
branes into an assortment
of fragments
ranging from quite large to small fragments
having a particle weight of only a few mil
lions. We have separated these fragments in
the ultracentrifuge
into fractions on the
basis of size. These fractions were analyzed
not only for their chemical composition, but
also their content of the respiratory-carrier
proteins. It was the remarkable finding that
all the fragments of the membrane, regard
less of size, contained complete sets of res
piratory carriers, in which the individual
carrier molecules were always a constant
fraction of the total protein content. From
this it follows that the respiratory assem
blies are probably uniformly disposed over
the molecular sheet which makes up the
]ENZYMES
\\
ATP
assem
do they comprise a significant proportion of
its substance. Calculations
show that the
catalytically active proteins of the respira
tory-chain assemblies may make up as much
as 40% of the mass of the inner mitochon
drial membrane. From this figure, we can
see at once that the molecular substance
comprising the mitochondrial
membrane is
not made simply of inert building blocks
1COUPLING
E―
these
blies are present entirely in the mitochon
drial membranes.
The next question is: Do these assemblies
make up only a very tiny fraction of the
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THE
472
CELL
LINES OF
FRAGMENT@T ION
@
TOP VIEW
LIPOPROTEIN
FABRIC
@—¿
RESPIRATORY
50
A
•¿ss
membrane (Fig. 10). Because the smallest
fragments also contained a complete set of
carrier molecules, it is presumed that the
mitochondrial
membrane
is made up of
recurring
units,
each
containing
a
functionally
complete
respiratory
assem
bly. Each catalytic unit is separated from
the next by relatively
@
fragile
lines of cleav
age, which are susceptible to mechanical or
chemical splitting. However, the chemical
and physical bonds holding the respiratory
carriers of the assembly together, within the
recurring unit, are very strong.
With this picture of the enzymic consti
tution of the mitochondrial
membranes in
hand, we can now proceed to consider still
another property which lends a whole new
dimension
of complexity to the enzymic
organization
of these membranes.
In the past year, we obtained evidence
that the mitochondrial membranes consti
tute a reversible contractile system, which
is driven
thyroxine
by ATP and in which
CROSS
OYISSSSSScnIYDOS..SS
FIG. 10. Schematic representation
many
ASSEMBLIES
of mitochondrial
SECTION
membrane.
of water. These swelling agents are: phos
phate, calcium ions, reduced glutathione,
and the hormone thyroxine. A wide variety
of other physiologic substances have been
tested, but only these four cause mitochon
drial swelling. Especially noteworthy is the
swelling caused by thyroxine, which is by
far the most potent agent, and is capable of
swelling mitochondria
in physiologic con
centrations.
Figure 11 shows some pertinent facts on
the swelling of mitochondria.
First, mito
chondria can swell in two general ways.
Since
they
have
two
membranes,
which
EMr@r@,4@4
I, i'ERMEABU
To
\
@j,O
SUC@toSE
\ it@ -iEi'@L@
To
\
\
SEI@OM
ALSUMIP4
@OL'(@U
GOSE
the hormone
plays a role. In this process,
as
it occurs in liver and kidney mitochondria,
large amounts of water may be transported
into or out of mitochondria
in a reversible
manner by the relaxation or contraction of
the mitochondnial membranes.
This investigation began with the finding
that there are four substances of physiologic
occurrence which will cause rapid swelling
of isolated liver or kidney mitochondria sus
pended in sucrose solutions through uptake
[email protected]
To
h@, I@o.
It'@PERMEA%L
E
1@o SocRos@
TWO
TyPES
SWELLII4ç
oF
Fic. 11. Permeability of mitochondrial membranes
and modes of swelling.
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SPECIAL ARTICLES
differ in permeability,
two different con
figurations of the mitochondria are formed.
Water, K@ and Na@ penetrate both mem
branes very rapidly. Sucrose, on the other
hand, penetrates the outer membrane very
rapidly,
but the inner membrane
only
slowly.
Serum
albumin,
polyvinyl
pyrroli
I-J
U)
swelling
with
a two-
to three-fold
a
I4
D520
U)
Li
0.4
done and polyglucose
do not penetrate
either membrane
readily. We found that
thyroxine causes a general increase in per
meability of the inner mitochondrial
mem
brane to a variety of substances; for exam
pie, sucrose. When mitochondria
undergo
such
0
60 p MOLES
ATP
in
MOLES H2O EXTRUDED
MOLES ATP SPLIT
crease in volume, they show increased rates
of oxidation, but a greatly reduced ability
to catalyze formation of ATP. Clearly the
volume
and degree
chondria
can
of swelling
dictate
their
of the mito
metabolic
ac
tivity.
Within the past year, we found that
swelling of mitochondria caused by thyrox
ine in this way may be reversed under con
ditions which are close to physiologic. If
the swelling takes place in a physiologic
medium high in potassium chloride, then
the swelling can be reversed with the ex
trusion of water simply by addition of ATP
(Fig. 12). In these experiments, the volume
0.6
P:O 2.8
P0=2.4
D520
=
390
60
20
MINUTES
FIG. 13. The relationship of AlP-splitting to water
extrusion by isolated mitochondria. It is seen that
hundreds of molecules of water may be extruded
per mole of ATP split.
of the mitochondrion
is an inverse function
of light transmission
through the suspen
sion. As can be seen, the volume of the
mitochondrion quickly returns to its original
value after addition of ATP.
The action of ATP in shrinking the mito
chondrion is entirely specific; no other sub
stance yet tested can replace it. Further
more, it has been found that the degree of
shrinking of the mitochondrion
is deter
mined by the concentration
of ATP added.
Another very important
point shown in
Figure 12 is that ATP
normal
when it
swollen
traction
piration
0.4
473
this
can restorenearly a
rate of oxidative phosphorylation
causes contraction of the thyroxine
mitochondria. The swelling and con
thus can produce changes in res
and phosphorylation,
implying that
cycle
may
be important
in metabolic
control.
20
We also measured the amounts of water
MINUTES
Ftc.12.Swellingof rat-liver
mitochondria
in the which are moved into and out of mitochon
dna during this cycle, by direct gravimetric
presence of thyroxine and their contractionby
ATP. The decrease in optical density corresponds
and isotopic procedures. At the beginning
to an increase
in water content,
and vice versa.
It is also seen that the P:O ratio declines during
swelling, but is restored again during the contrac
tion stage. However,
the mitochondria
lose DPN
and also their respiratory
response
to ADP after
drastic swelling.
of such an experiment (Fig.13),thyroxineis
added and the mitochondnia
swell, as is
shown by the drop in the optical trace. Di
rect
measurement
of the
water
ing swelling shows that 780
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uptake
dur
@moleof water
THE
474
entered
mately
the mitochondria,
which approxi
doubled
their volume. On addition
of ATP, the mitochondria
went
contraction
with
promptly
extrusion
under
of water,
as is shown by the optical trace. About 650
p.moles
of water
were
extruded
on adding
only 60 @moleof ATP.
Actually only a very small fraction of the
added ATP undergoes
splitting during con
traction
of the mitochondria.
As can be
seen, only 1 or 2 p.moles of ATP are split
(luring the contraction,
and as soon as con
traction
ceases the hydrolysis
of ATP also
stops. These findings show that the mito
chondria thus can extrude several hundred
molecules of water for each molecule of
ATP split. These
which
cannot
sistent
with
system
in the
squeeze
facts,
together
be discussed
the
water
existence
membranes
and other
with others
here, are con
of a contractile
that
can
literally
small molecules
FIG. 14. Arrangement
CELL
out
the
These
mitochondria
1w mechanical
findings
have
the
biochemical
approach
encouraged
and
us
to
enzymic
basis of the contractile
mechanism.
It has
been found
that when ATP is added
to
fragments
of the mitochondrial
membrane,
they do not absorb and extrude water, but
they do change their shape in the presence
of ATP. We have also found that the con
tractile enzymes in the mitochondrial
mem
brane are probably
identical
with one or
more
of the
intermediate
coupling
enzymes
of the respiratory
chain, because
the con
traction of the mitochondria
is inhibited
by
certain agents which can also uncouple
oxi
dative
phosphorylation,
such as azide,
or
polyhydroxylic
molecules such as sucrose. If
we again look at a respiratory
assembly (Fig.
9), this finding
means
that one of the
phosphate-coupling
enzyme
molecules
in
of mitochondria
(after
of
means.
in the renal tubule
Rhodin).
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cell
SPF@C!AL A@TI@LF@S
475
the assembly may be “¿mechano-enzyme― for thyroxine, but I will not be so foolhardy
which changes shape depending on whether
as to insist that these effects are a full ex
or not it is phosphorylated.
This change of planation of the physiologic action of the
hormone.
shape presumably causes contraction of the
membrane.
Figure 14 is a diagram
of the configura
tion of a renal tubule cell,as deduced by
The mitochondnial membrane is not only
Rhodin from electron micrographs
of kidney
a complex electron-carrying
and phosphory
lation enzyme system capable of converting
sections. It is seen that the mitochondria
energy of oxidation into ATP, but also is are aligned in the direction of transport of
a mechanoenzyme
system capable of water and solutes between blood and urine;
suggests the mitochondnia
changes of dimension and permeability. this arrangement
are not only the power supply for active
These experiments also show that the meta
transport,
but they may also be active
bolic activities of the mitochondrion
are
vehicles for the transport of water and elec
greatly affected by its geometrical config
trolytes. Although the research on mito
uration and the degree of swelling. These
interrelationships
permit the possibility of a chondnial structure and function I have de
scribed
is perhaps
far removed
from the
number of control mechanisms, of a feed
back nature, governing the availability of clinic, yet the transport functions of the
fuel for the mitochondnia, its oxidative utili
renal tubule cell are surely of daily sig
zation and the formation of ATP. The ex
nificance
in the practice
of pediatric
medi
periments also suggest a physiologic role
cine.
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THE ENZYMIC AND MORPHOLOGIC ORGANIZATION OF THE
MITOCHONDRIA
Albert L. Lehninger
Pediatrics 1960;26;466
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
Copyright © 1960 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005.
Online ISSN: 1098-4275.
Downloaded from by guest on June 15, 2017
THE ENZYMIC AND MORPHOLOGIC ORGANIZATION OF THE
MITOCHONDRIA
Albert L. Lehninger
Pediatrics 1960;26;466
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
/content/26/3/466
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,
it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked
by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,
Illinois, 60007. Copyright © 1960 by the American Academy of Pediatrics. All rights reserved. Print
ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from by guest on June 15, 2017