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MITOCÔNDRIAS 
Edson Rosa Pimentel 
Mitocôndrias – túbulo renal – Coloração de Régaud 
A 
B C 
A: suprarenal 
 
B: epidídimo 
 
C: Célula adiposa de 
 morcego hibernando 
A 
B C 
Mitocôndrias em 
espermatozóide (A), 
e em célula muscular (B,C). 
 
Mitochondrial fission and fusion. These processes involve both outer 
and inner mitochondrial membranes. (A) During fusion and fission, both 
matrix and intermembrane space compartments are maintained. Different 
membrane fusion machines are thought to operate at the outer and inner 
membranes. Conceptually, the fission process resembles that of bacterial 
cell division. The pathway shown has been postulated from static views 
such as that shown in (B). (B) An electron micrograph of a dividing 
mitochondrion in a liver cell. (B, courtesy of Daniel S. Friend.) 
Dynamic mitochondrial reticulum. (A) In yeast cells, mitochondria form a 
continuous reticulum underlying the plasma membrane. (B) A balance 
between fission and fusion determines the arrangement of the mitochondria in 
different cells. (C) Time-lapse fluorescent microscopy shows the dynamic 
behavior of the mitochondrial network in a yeast cell. In addition to shape 
changes, the network is constantly remodeled by fission and fusion (red 
arrows). The pictures were taken at 3-minute intervals. (A and C, from J. 
Nunnari et al., Mol. Biol. Cell 8:1233 1242, 1997, with permission by the 
American Society for Cell Biology.) 
Interação entre mitocôndria e microtúbulos em célula humana em 
cultura. A: célula tratada com rodamina mostrando mitocôndria. B: 
mesma célula com imunofluorescência para microtúbulo. 
Tamanho de 
mitocôndria, 
bactéria e 
cloroplasto 
COMPOSIÇÃO QUÍMICA 
MÉTODOS DE ESTUDO 
 
 
Membrana externa: 50% proteínas e 50% lipídios. 
 Porina. 
 
Membrana interna: 80% proteínas e 20% lipídios 
 Componentes da cadeia respiratória 
 Succinato desidrogeanse 
 ATP sintase 
 Cardiolipina 
 
Matriz : DNA e RNA 
 Ribonucleoproteínas e enzimas para a síntese protéica 
 Enzimas das reações do ciclo de Krebs, da -oxidação dos ácidos 
 graxos, do metabolismo dos compostos aminados. 
 Enzimas para hidroxilação de intermediários da síntese de 
hormônios esteróides. 
 DNA e RNA polimerase. 
Composição Química 
The structure of 
cardiolipin. Cardiolipin is 
an unusual lipid in the inner 
mitochondrial membrane. 
Mitochondrial and nuclear DNA stained with a fluorescent dye. This 
micrograph shows the distribution of the nuclear genome (red) and the multiple 
small mitochondrial genomes (bright yellow spots) in a Euglena gracilis cell. The 
DNA is stained with ethidium bromide, a fluorescent dye that emits red light. In 
addition, the mitochondrial matrix space is stained with a green fluorescent dye 
that reveals the mitochondria as a branched network extending throughout the 
cytosol. The superposition of the green matrix and the red DNA gives the 
mitochondrial genomes their yellow color. (Courtesy of Y. Hayashi and K. Ueda, 
J. Cell Sci. 93:565 570, 1989. © The Company of Biologists.) 
The production of mitochondrial and chloroplast proteins by 
two separate genetic systems. Most of the proteins in these 
organelles are encoded by the nucleus and must be imported 
from the cytosol. 
An electron micrograph of an 
animal mitochondrial DNA 
molecule caught during the 
process of DNA replication. The 
circular DNA genome has 
replicated only between the two 
points marked by red arrows. The 
newly synthesized DNA is colored 
yellow. (Courtesy of David A. 
Clayton.) 
ORIGEM 
Some major events that are believed to have occurred during the evolution 
of living organisms on earth. 
A suggested evolutionary pathway for the origin of mitochondria. 
Argumentos favoráveis à hipótese 
simbiótica 
1. DNA mitocondrial é circular como o DNA das bactérias. 
 
2. A síntese protéica das mitocôndrias é inibida por cloranfenicol como ocorre com 
as bactérias. 
 
3. O coeficiente de sedimentação dos ribossomos de mitocôndrias (55S) é mais 
próximo de bactérias (70S) do que de eucariotos (80S). 
 
4. A síntese protéica em mitocôndrias se inicia com formil-metionina como ocorre 
em bactérias. 
 
 
 
 
 
GENOMA, PROTEÍNAS E 
RNAs 
The organization of the human mitochondrial genome. The genome 
contains 2 rRNA genes, 22 tRNA genes, and 13 protein-coding sequences. The 
DNAs of many other animal mitochondrial genomes have also been completely 
sequenced. Most of these animal mitochondrial DNAs encode precisely the 
same genes as humans, with the gene order being identical for animals that 
range from mammals to fish. 
Electron micrographs of 
yeast cells. (A) The structure 
of normal mitochondria. (B) 
Mitochondria in a petite 
mutant. In petite mutants, all 
the mitochondrion-encoded 
gene products are missing, 
and the organelle is 
constructed entirely from 
nucleus-encoded proteins. 
(Courtesy of Barbara 
Stevens.) 
The origins of mitochondrial 
RNAs and proteins. The 
proteins encoded in the nucleus 
and imported from the cytosol 
have a major role in creating the 
genetic system of the 
mitochondrion, in addition to 
contributing most of the 
organelle's other proteins. Not 
indicated in this diagram are the 
additional nucleus-encoded 
proteins that regulate the 
expression of individual 
mitochondrial genes at 
posttranscriptional levels. The 
mitochondrion itself contributes 
only mRNAs, rRNAs, and tRNAs 
to its genetic system. 
FISIOLOGIA 
Simplified diagram of the three stages 
of cellular metabolism that lead from 
food to waste products in animal cells. 
This series of reactions produces ATP, 
which is then used to drive biosynthetic 
reactions and other energy-requiring 
processes in the cell. Stage 1 occurs 
outside cells. Stage 2 occurs mainly in the 
cytosol, except for the final step of 
conversion of pyruvate to acetyl groups on 
acetyl CoA, which occurs in 
mitochondria. Stage 3 occurs in 
mitochondria. 
An outline of glycolysis. Each of 
the 10 steps shown is catalyzed by a 
different enzyme. Note that step 4 
cleaves a six-carbon sugar into two 
three-carbon sugars, so that the 
number of molecules at every stage 
after this doubles. As indicated, step 
6 begins the energy generation 
phase of glycolysis, which causes 
the net synthesis of ATP and NADH 
molecules (see also Panel 2-8). 
The structure of the important activated carrier molecule acetyl CoA. A 
space-filling model is shown above the structure. The sulfur atom (yellow) forms 
a thioester bond to acetate. Because this is a high-energy linkage, releasing a 
large amount of free energy when it is hydrolyzed, the acetate molecule can be 
readily transferred to other molecules. 
How electrons are donated by NADH. In this diagram, the high-energy 
electrons are shown as two red dots on a yellow hydrogen atom. A hydride ion 
(H- a hydrogen atom and an extra electron) is removed from NADH and is 
converted into a proton and two high-energy electrons: H- H+ + 2e-. Only the 
ring that carries the electrons in a high-energy linkage is shown. Electrons are 
also carried ina similar way by FADH2. 
The path of electrons through the three respiratory enzyme complexes. The 
relative size and shape of each complex are shown. During the transfer of 
electrons from NADH to oxygen (red lines), ubiquinone and cytochrome c serve 
as mobile carriers that ferry electrons from one complex to the next. As indicated, 
protons are pumped across the membrane by each of the respiratory enzyme 
complexes. 
Quinone electron carriers. Ubiquinone in the respiratory chain picks up one H+ 
from the aqueous environment for every electron it accepts, and it can carry either 
one or two electrons as part of a hydrogen atom (yellow). When reduced 
ubiquinone donates its electrons to the next carrier in the chain, these protons are 
released. A long hydrophobic tail confines ubiquinone to the membrane and 
consists of 6 10 five-carbon isoprene units, the number depending on the 
organism. The corresponding electron carrier in the photosynthetic membranes of 
chloroplasts is plastoquinone, which is almost identical in structure. For simplicity, 
both ubiquinone and plastoquinone are referred to in this chapter as quinone 
(abbreviated as Q). 
The structure of the heme group 
attached covalently to 
cytochrome c. The porphyrin ring 
is shown in blue. There are five 
different cytochromes in the 
respiratory chain. Because the 
hemes in different cytochromes 
have slightly different structures 
and are held by their respective 
proteins in different ways, each of 
the cytochromes has a different 
affinity for an electron. 
Fosforilação Oxidativa 
Chemiosmotic coupling. Energy 
from sunlight or the oxidation of 
foodstuffs is first used to create an 
electrochemical proton gradient 
across a membrane. This gradient 
serves as a versatile energy store 
and is used to drive a variety of 
energy-requiring reactions in 
mitochondria, chloroplasts, and 
bacteria. 
The general mechanism of oxidative phosphorylation. (A) As a high-energy 
electron is passed along the electron-transport chain, some of the energy 
released is used to drive the three respiratory enzyme complexes that pump H+ 
out of the matrix. The resulting electrochemical proton gradient across the inner 
membrane drives H+ back through the ATP synthase, a transmembrane protein 
complex that uses the energy of the H+ flow to synthesize ATP from ADP and Pi 
in the matrix. (B) An electron micrograph of the inside surface of the inner 
mitochondrial membrane in a plant cell. Densely packed particles are visible, 
due to protruding portions of the ATP synthases and the respiratory enzyme 
complexes. (Micrograph courtesy of Brian Wells.) 
 
 
Hipótese Quimiosmótica (Peter Mitchell, 1961) 
 
 
A membrana interna da mitocôndria precisa estar intacta para que a 
fosforilação oxidativa ocorra. 
 
Os carreadores de elétrons da cadeia respiratória servem como um 
sistema de transporte ativo para transportar prótons da matriz para o 
espaço intermembranas, gerando um gradiente de prótons. 
 
O gradiente de prótons gerado, é usado para sintetizar ATP. 
A general model for H+ pumping. This model for H+ pumping by a 
transmembrane protein is based on mechanisms that are thought to be used by 
both cytochrome oxidase and bacteriorhodopsin. The protein is driven through a 
cycle of three conformations: A, B, and C. As indicated by their vertical spacing, 
these protein conformations have different energies. In conformation A, the 
protein has a high affinity for H+, causing it to pick up a H+ on the inside of the 
membrane. In conformation C, the protein has a low affinity for H+, causing it to 
release a H+ on the outside of the membrane. The transition from conformation B 
to conformation C that releases the H+ is energetically unfavorable, and it occurs 
only because it is driven by being allosterically coupled to an energetically 
favorable reaction occurring elsewhere on the protein (blue arrow). 
 
 
The ATP synthase is a reversible coupling device 
that can convert the energy of the electrochemical 
proton gradient into chemical-bond energy, or vice 
versa. The ATP synthase can either (A) synthesize 
ATP by harnessing the proton-motive force or (B) 
pump protons against their electrochemical gradient 
by hydrolyzing ATP. 
ATP synthase. (A) The enzyme is composed of a head portion, called the F1 
ATPase, and a transmembrane H+ carrier, called F0. Both F1 and F0 are 
formed from multiple subunits, as indicated. A rotating stalk turns with a rotor 
formed by a ring of 10 to 14 c subunits in the membrane (red). The stator 
(green) is formed from transmembrane a subunits, tied to other subunits that 
create an elongated arm. This arm fixes the stator to a ring of 3a and 3b 
subunits that forms the head. (B) The three-dimensional structure of the F1 
ATPase, determined by x-ray crystallography. This part of the ATP synthase 
derives its name from its ability to carry out the reverse of the ATP synthesis 
reaction namely, the hydrolysis of ATP to ADP and Pi, when detached from the 
transmembrane portion. Nature 370:621 628, 1994. 
The binding-change mechanism of ATP synthesis from ADP and Pi by the 
F0F1 complex. The three  subunits alternate between three conformational 
states that differ in their binding affinities for ATP, ADP, and Pi. Step 1 : After ADP 
and Pi bind to one of the three  subunits (here, arbitrarily designated 1) whose 
nucleotide-binding site is in the O (open) conformation, proton flux powers a 120° 
rotation of the g subunit (relative to the fixed  subunits). This causes an increase 
in the binding affinity of the 1 subunit for ADP and Pi to L (low), an increase in the 
binding affinity of the 3 subunit for ADP and Pi from L to T (tight), and a decrease 
in the binding affinity of the 2 subunit for ATP from T to O, causing release of the 
bound ATP. Step 2 : The ADP and Pi in the T site (here the 3 subunit) form ATP, a 
reaction that does not require an input of energy, and ADP and Pi bind to the 2 
subunit, which is in the O state. This generates an F1 complex identical with that 
which started the process (upper left) except that it is rotated 120°. Step 1 now 
occurs again, and the cycling of the O L → T → O conformations of each  
subunit continues. [Adapted from P. Boyer, 1989, FASEB J. 3:2164, and Y. Zhou 
et al., 1997, Proc. Nat'l. Acad. Sci. USA 94:10583.] 
 
Rendimento de ATP na mitocôndria 
• De glicose até Piruvato: 2 moléculas de ATP 
• Cada NADH que cede 1 par de elétrons na cadeia respiratória rende em média 2,5 
moléculas de ATP. 
• Cada FADH2 que cede um par de elétrons na cadeia respiratória rende em média 1,5 
molécula de ATP. 
• Cada 2 moléculas de Piruvato que entram mitocôndria produzem 2 acetil CoA que 
geram 2 NADH, que ao cederem elétrons na cadeia respiratória produzem 5 
moléculas de ATP 
• Cada acetil-CoA que entra no Ciclo de Krebs produz uma molécula de GTP que logo 
se transforma em ATP. 
• Como no ciclo de Krebs são produzidos 3 NADH e 1 FADH2 e 1 ATP para cada 
Piruvato/Acetil CoA, teremos uma produção de (3x2,5) + (1x1,5) + 1 = 10 moléculas 
de ATP. Como são dois Acetil CoA, então a produção de ATP é de 20 moléculas de 
ATP. 
• Considerando os elétrons provenientes das 2 moleçulas de NADH produzidas na 
glicólise , teremos mais 2x2,5 moléculas de ATP, mais o rendimento de 2 moleculas 
de ATP na glicólise. 
• Assim para cada molécula de glicose podem ser produzidas 32 moléculas de ATP. 
 
 
 
 
Some of the active transport processes driven by the 
electrochemical proton gradient across the inner 
mitochondrialmembrane. Pyruvate, inorganic 
phosphate (Pi), and ADP are moved into the matrix, while 
ATP is pumped out. The charge on each of the 
transported molecules is indicated for comparison with the 
membrane potential, which is negative inside, as shown. 
The outer membrane is freely permeable to all of these 
compounds. 
Entrada de ácido graxo na mitocôndria 
Síntese de hormônio esteróide 
Doenças mitocondriais 
 Neuropatia optica hereditária de Leber 
 Devido mutação no DNA mitocondrial , afeta o complexo I (NADH 
desidrogenase, substitui uma His por Arg) do sistema de transporte 
de elétrons. Outra mutação que também afeta esse complexo pode 
causar desordem muscular. (Cooper – The Cell) 
 
 Epilepsia mioclonica e doença da fibra vermelha irregular 
(MERRF). 
 Causada por uma mutação em um dos genes que produzem RNAt 
mitocondrial, levando a uma diminuiç ão na síntese de proteínas 
mitocondriais responsáveis pelo transporte de elétrons e produção 
de ATP. 
 
Resumo de Mitocôndria 
1. Não podem ser vistas com detalhes no microscópio ótico. 
 
2. Tem duas membranas sendo que a interna é bem mais seletiva do que a 
externa. 
 
3. Tem DNA, RNA e ribossomos. 
 
4. Origem: Teoria Simbiótica. 
 
5. Funções: Respiração celular aeróbica, síntese de ATP, β-oxidação de ácidos 
graxos, participa da síntese de hormônios esteróides, participa do ciclo da 
uréia. 
 
6. Piruvato Desidrogenase: Piruvato é descaboxilado e desidrogenado 
gerando Acetil-Coa. 
 
7. Ciclo de Krebs: Acetil-Coa entra no ciclo de Krebs. Várias reações ocorrem 
resultando em 3 NADH + H+ e 1 FADH2 , 1 ATP e 2 descarboxilações, para 
cada acetil-CoA que entra no ciclo de Krebs. 
 
8. NADH + H+ e FADH2 cedem seus elétrons para a cadeia respiratória 
resultando em ejeção de prótons e redução de O2 que então resulta em 
formação de água. 
 
9. Fosforilação oxidativa do ADP formando ATP. 
 
10. β-oxidação de ácidos graxos resulta em liberação de Acetil-CoA, que entra 
no ciclo de Krebs. 
 
11. Rendimento de produção de ATP por molécula de glicose: 30 ou 32 
moléculas de ATP.

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