mitochondria.html 17.4 KB
Newer Older
Vesa Oikonen's avatar
Vesa Oikonen committed
1
2
3
---
title: Mitochondria
author: Vesa Oikonen
Vesa Oikonen's avatar
ref    
Vesa Oikonen committed
4
updated_at: 2021-04-27
Vesa Oikonen's avatar
Vesa Oikonen committed
5
6
7
created_at: 2017-09-20
tags:
  - Mitochondria
Vesa Oikonen's avatar
Vesa Oikonen committed
8
9
  - Oxygen
  - Oxidative stress
Vesa Oikonen's avatar
Vesa Oikonen committed
10
11
12
13
---

<h1>Mitochondria in PET studies</h1>

Vesa Oikonen's avatar
Vesa Oikonen committed
14
<p>Mitochondrion is a cell organelle in eukaryotes, originally endosymbiotic prokaryotic cell. 
Vesa Oikonen's avatar
links    
Vesa Oikonen committed
15
Mitochondria are present in all cells, except mature <a href="./rbc.html">red blood cells</a>, 
16
17
18
19
20
21
but their number, size, and shape is highly variable. The highest mitochondrial content is found in 
<a href="./organ_heart.html">the heart</a> and <a href="./organ_kidney.html">kidneys</a>, which 
also are the organs with the highest resting metabolic rates.
Mitochondria are dynamic organelles, constantly undergoing fusion and fission, in association with 
the cytoskeleton and endoplasmic reticulum. <em>Mitophagy</em> is the process of selective removal 
of dysfunctional mitochondria from cells by autophagy. <em>Mitochondrial homeostasis</em> requires
vesoik@utu.fi's avatar
vesoik@utu.fi committed
22
that these processes are in dynamic balance, as required by changing metabolic conditions.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
23
24
25

<h2>Structure</h2>

Vesa Oikonen's avatar
Vesa Oikonen committed
26
27
28
<p>Mitochondrion has two membranes, the outer membrane, and and the inner membrane, which is highly 
compartmentalized with infoldings (cristae), with surface area several folds larger than the 
outer membrane. The space within the inner membrane (matrix) contains mitochondrial ribosomes,
vesoik@utu.fi's avatar
vesoik@utu.fi committed
29
several copies of mitochondrial DNA, and a highly concentrated mixture of hundreds of enzymes.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
30
31
32
33
34
35
36
37
38

<p>The outer mitochondrial membrane resembles cellular plasma membranes, except that the large 
number of porins allow free diffusion of small molecules and even small proteins across it. 
Therefore the solute concentrations in the cytoplasm and in mitochondrial intermembrane space 
(perimitochondrial space) are the same, but protein contents are different; for example 
<em>cytochrome c</em> is located in the intermembrane space only.
Endoplasmic reticulum (ER) associates with large fraction of the mitochondrial outer membrane 
(mitochondria-associated ER-membrane, MAM); it has a critical role in cellular homeostasis, 
for example via involvement in Ca<sup>2+</sup> signalling; it is also crucial in lipid and lipid 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
39
intermediate transfer between mitochondria and ER.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
40

Vesa Oikonen's avatar
Vesa Oikonen committed
41
42
<p>The inner mitochondrial membrane has unique phospholipid content, including 
<a href="#cardiolipin">cardiolipin</a>, that is not found elsewhere. 
Vesa Oikonen's avatar
Vesa Oikonen committed
43
Proteins make up about 75% of the mass of the inner membrane, regulating strictly the transport of 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
44
45
solutes between perimitochondrial space and matrix.</p>

Vesa Oikonen's avatar
Vesa Oikonen committed
46
47
48

<h2>Genetic system</h2>

Vesa Oikonen's avatar
Vesa Oikonen committed
49
50
<p>The mitochondrial genomes in animal cells are small, less than 1/10 of the size in plants. 
Human mitochondrial DNA (mtDNA, mDNA) contains only 37 genes, which encode for rRNAs, tRNAs, and 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
51
13 proteins. Most of the components of mitochondria are encoded by nuclear DNA.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
52

Vesa Oikonen's avatar
Vesa Oikonen committed
53
54
55
56
57
58
<p>All mitochondria, and thus also mtDNA, are contributed by the oocyte, not by the sperm 
(maternal inheritance); mutations in mtDNA are therefore transmitted to the next generation by 
the mother. It is possible that only part of the mitochondria, or part of the mtDNA inside one 
mitochondrion, are defective. During cell division, the mitochondria segregate randomly between 
the two new cells. During embryonic development the cells carrying defective mitochondria
may end up in different organs, causing variable symptoms, like in MELAS. Some mutations are seldom 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
59
inherited but occur spontaneously, such as mtDNA deletions in Kearns-Sayre syndrome.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
60

Vesa Oikonen's avatar
Vesa Oikonen committed
61
62
<p>Progressive accumulation of mutations in mtDNA may contribute to the ageing process. 
Mitochondrial genome lacks histones and introns.
Vesa Oikonen's avatar
Vesa Oikonen committed
63
64
Mitochondria have less effective DNA error checking capability than nuclear DNA. However, 
mtDNA is well protected against DNA damage by proteins and the multiple copies of mtDNA.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
65
66

<p>Mitochondrial disorders can also be caused by mutations of the nuclear DNA,
vesoik@utu.fi's avatar
vesoik@utu.fi committed
67
68
in genes that code for mitochondrial components.</p>

Vesa Oikonen's avatar
Vesa Oikonen committed
69

vesoik@utu.fi's avatar
vesoik@utu.fi committed
70
<h2><a name="function">Function</a></h2>
Vesa Oikonen's avatar
Vesa Oikonen committed
71

vesoik@utu.fi's avatar
vesoik@utu.fi committed
72
<p><a href="./target_fatty-acid.html">Fatty acids</a> are broken down in <em>beta oxidation</em> in 
Vesa Oikonen's avatar
Vesa Oikonen committed
73
74
the inner mitochondrial membrane to produce acetyl-CoA for the citric acid cycle.
Glycolysis in the cytoplasm produces pyruvate, which is oxidized and converted to acetyl-CoA, 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
75
also in the inner mitochondrial membrane and matrix.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
76

Vesa Oikonen's avatar
Vesa Oikonen committed
77
78
79
<p><a name="cac">Citric acid cycle</a> (CAC, tricarboxylic acid cycle, Kreb cycle) occurs in 
the mitochondrial matrix, oxidizing the acetyl in acetyl-CoA to CO<sub>2</sub>.
CAC provides cells with essential precursors for synthesis of amino acids and other molecules, 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
80
and NADH, FADH<sub>2</sub>, and succinate for the oxidative phosphorylation pathway.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
81

Vesa Oikonen's avatar
Vesa Oikonen committed
82
83
<p><em>Oxidative phosphorylation pathway</em> produces ATP. Inner mitochondrial membrane contains 
the components of <em>electron transport chain</em>, where electrons are transferred in redox 
Vesa Oikonen's avatar
Vesa Oikonen committed
84
85
86
87
reactions from NADH to <a href="./o2.html">oxygen</a>, and the energy is used to create 
an electrochemical gradient across the membrane by pumping H<sup>+</sup> (protons) out of 
the matrix, creating negative charge in the inner side of the membrane. 
ATP synthase uses the H<sup>+</sup> gradient to produce ATP.
Vesa Oikonen's avatar
Vesa Oikonen committed
88
89
The solubility of O<sub>2</sub> is highest in the centre of lipid bilayer, and the diffusion of 
oxygen to the binding site of cytochrome c oxidase (COX) at the centre of the inner membrane 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
90
bilayer is the last step of oxygen transport in the respiratory cycle.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
91

Vesa Oikonen's avatar
Vesa Oikonen committed
92
93
94
95
<p>Cells can regulate the number of proton leaking ion channels on the inner membrane. These
<em>uncoupling proteins</em> (UCPs) reduce the proton gradient and production of ATP, thus
uncoupling the ATP synthesis from substrate oxidation. 
UCP1 is present in <a href="./organ_bat.html">brown adipose tissue</a>, required for its thermogenic 
96
97
function. UCP2 is present in tissues such as <a href="./organ_kidney.html">kidneys</a> that have 
high ATP production. Oxidative stress and hyperglycaemia induce expression of UCP2 and UCP3.
Vesa Oikonen's avatar
ref    
Vesa Oikonen committed
98
In cardiomyocytes the expression patterns of UCP2 and UCP3 reflect the metabolic type
vesoik@utu.fi's avatar
vesoik@utu.fi committed
99
(<a href="https://doi.org/10.3389/fphys.2018.00747">Hilse et al., 2018</a>).</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
100

Vesa Oikonen's avatar
Vesa Oikonen committed
101
<p>Reduction of oxygen in the oxidative phosphorylation pathway involves potentially harmful 
Vesa Oikonen's avatar
Vesa Oikonen committed
102
intermediates, <a href="#ROS">reactive oxygen species (ROS)</a>.
Vesa Oikonen's avatar
Vesa Oikonen committed
103
Under normal conditions about 0.1-0.2% of oxygen consumption in mitochondria results into production 
104
105
106
of ROS. ROS have also signalling functions, affecting for example vascular tone. 
Mitochondria have an important role in regulation of <a href="./target_inflammation.html"
>inflammation</a> (<a href="https://doi.org/10.3389/fimmu.2018.00536">Meyer et al., 2018</a>)
vesoik@utu.fi's avatar
vesoik@utu.fi committed
107
and <a href="./target_apoptosis.html">apoptosis</a>.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
108

Vesa Oikonen's avatar
Vesa Oikonen committed
109
110
111
112
113
114
115
116
<p><a name="cardiolipin">Cardiolipin</a> in the inner mitochondrial membrane contains four fatty 
acids, and is otherwise found only in bacterial cell membranes. 
Cardiolipin is involved in regulation of electron transport chain assembly and function, 
ATP synthesis, and apoptosis. Peroxidation of cardiolipin destabilizes electron transport chain, 
increasing <a href="#ROS">ROS</a> production further. 
<a name="elamipretide">Elamipretide</a> (Bendavia) is a tetrapeptide drug that selectively binds to 
and stabilizes cardiolipin, reduces ROS production, and prevents apoptosis.</p>

Vesa Oikonen's avatar
Vesa Oikonen committed
117

Vesa Oikonen's avatar
Vesa Oikonen committed
118
<h3><a name="ROS">Reactive oxygen species</a></h3>
Vesa Oikonen's avatar
Vesa Oikonen committed
119

Vesa Oikonen's avatar
Vesa Oikonen committed
120
<p>NADPH oxidases are the main producers of <a href="./ros.html">ROS</a> in mitochondria.
Vesa Oikonen's avatar
Vesa Oikonen committed
121
122
Mitochondrial SOD-1 and SOD-2 scavenges superoxide into oxygen and hydrogen peroxide, but 
high ROS production can disrupt mitochondrial membranes, leading to decreased activity of SODs.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
123

Vesa Oikonen's avatar
Vesa Oikonen committed
124
<p>Mitochondrial outer membrane contains monoamine oxidase (MAO), which oxidizes monoamines, such as 
Vesa Oikonen's avatar
Vesa Oikonen committed
125
dopamine and noradrenaline, and produces hydrogen peroxide in the process.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
126

Vesa Oikonen's avatar
Vesa Oikonen committed
127
128
129
130
<p>The inner membrane of mitochondria contain angiotensin II type 2 receptors
(components of <a href="./organ_kidney.html#RAAS">RAAS</a>), which, when activated,
increases mitochondrial membrane potential and ROS production.</p>

Vesa Oikonen's avatar
Vesa Oikonen committed
131
132
133
<p><sup>64</sup>Cu- or <sup>62</sup>Cu-labelled Cu-ATSM is used to measure tissue 
<a href="./target_hypoxia.html#redox">hypoxia</a>, but since its accumulation mechanism is based on 
the electron rich environment induced by mitochondrial impairment, it can represent the oxidative 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
134
135
136
stress state (<a href="https://www.ncbi.nlm.nih.gov/pubmed/25366710">Okazawa et al., 2014</a>). 
It has been used for example in a PET study of ALS patients 
(<a href="https://doi.org/10.1212/WNL.0000000000001588">Ikawa et al., 2015</a>).</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
137
138
139
140


<h3><a name="MC-I">MC-I activity</a></h3>

Vesa Oikonen's avatar
Vesa Oikonen committed
141
142
143
144
<p>Mitochondrial complex I (MC-I, NADH dehydrogenase, NADH-coenzyme Q oxidoreductase) is the first 
and largest component in the electron transport chain.
Oxidative phosphorylation, and thus MC-I, is usually very active in metabolically active cells, but 
activated inflammatory cells and cancer cells typically have reduced oxidative phosphorylation, and 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
145
146
147
produce ATP by converting <a href="./glucose.html">glucose</a> into 
<a href="./analysis_11c-lactate.html">lactate</a> instead, despite of availability of 
<a href="./o2.html">oxygen</a> (aerobic glycolysis, Warburg effect).</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
148
149
150
151
152
153
154
155

<p><a href="./analysis_18f-flurpiridaz.html">[<sup>18</sup>F]Flurpiridaz</a> (BMS-747158-02, 
[<sup>18</sup>F]BMS-747158-01, [<sup>18</sup>F]BMS) is a structural analogue of the insecticide 
pyridaben, which competes for MC-1 binding with ubiquinone.
In the <a href="./organ_heart.html">heart</a> oxidative phosphorylation is very active and 
the density of mitochondria is high; the uptake of [<sup>18</sup>F]Flurpiridaz is nearly 
irreversible, and limited by blood flow, in the myocardium. Therefore, this tracer has been used to 
measure myocardial perfusion. However, in other organs, the uptake of [<sup>18</sup>F]Flurpiridaz
Vesa Oikonen's avatar
Vesa Oikonen committed
156
may represent the activity (or concentration) of MC-I.
Vesa Oikonen's avatar
ref    
Vesa Oikonen committed
157
158
159
Mitochondrial dysfunction in the mouse model of <a href="./dis_mets.html#NASH">NASH</a> can be seen
as reduced [<sup>18</sup>F]Flurpiridaz uptake in <a href="./organ_liver.html">the liver</a> 
(<a href="https://doi.org/10.1186/s13550-017-0345-5">Rokugawa et al., 2017</a>).
Vesa Oikonen's avatar
Vesa Oikonen committed
160
161
Neuronal damage after ischemia can be observed with this tracer, although relatively high 
nonspecific uptake in the brain has led the researchers to develop other analogues 
Vesa Oikonen's avatar
Vesa Oikonen committed
162
163
(<a href="https://doi.org/10.2967/jnumed.113.125328">Tsukada et al., 2014</a>).</p>

vesoik@utu.fi's avatar
vesoik@utu.fi committed
164
<p>[<sup>18</sup>F]-BCPP-EF has shown promise in <a href="./organ_brain.html">the brain</a> imaging 
vesoik@utu.fi's avatar
link    
vesoik@utu.fi committed
165
of <a href="./dis_stroke.html">stroke</a>, ageing, and dementia 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
166
167
168
169
(Tsukada et al., <a href="https://doi.org/10.1016/B978-0-12-801415-8.00020-5">2014a</a>,
<a href="https://doi.org/10.1007/s00259-013-2628-z">2014b</a>,
<a href="https://doi.org/10.1038/jcbfm.2014.5">2014c</a>,
<a href="https://doi.org/10.2967/jnumed.115.169615">2016</a>;
Vesa Oikonen's avatar
Vesa Oikonen committed
170
<a href="https://doi.org/10.1002/syn.21842 ">Nishiyama et al., 2015</a>;
Vesa Oikonen's avatar
ref    
Vesa Oikonen committed
171
<a href="https://doi.org/10.1038/srep30127">Fukuta et al., 2016</a>;
vesoik@utu.fi's avatar
ref    
vesoik@utu.fi committed
172
<a href="https://doi.org/10.2967/jnumed.119.228080">Mansur et al., 2020</a>),
Vesa Oikonen's avatar
Vesa Oikonen committed
173
174
and in early detection of radiotherapy effect 
(<a href="https://doi.org/10.1371/journal.pone.0170911">Murayama et al., 2017</a>).
Vesa Oikonen's avatar
Vesa Oikonen committed
175
[<sup>18</sup>F]-BCPP-BF may be useful in detection of impaired MC-I activity
vesoik@utu.fi's avatar
vesoik@utu.fi committed
176
177
178
in <a href="./organ_liver.html">liver</a> and <a href="./organ_kidney.html">kidneys</a> 
(<a href="https://doi.org/10.1186/s13550-016-0241-4">Ohba et al., 2016</a>;
<a href="https://doi.org/10.1186/s13550-018-0420-6">Sakai et al., 2018</a>).</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
179
180

<p>Rotenone is another inhibitor of MC-I, used as an organic pesticide.
Vesa Oikonen's avatar
Vesa Oikonen committed
181
182
<sup>18</sup>F-labeled rotenone derivative, [<sup>18</sup>F]FDHR, has been developed to be used as 
myocardial perfusion tracer 
vesoik@utu.fi's avatar
vesoik@utu.fi committed
183
(<a href="https://www.ncbi.nlm.nih.gov/pubmed/15534068">Marshall et al., 2004</a>).</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
184
185


Vesa Oikonen's avatar
Vesa Oikonen committed
186
<h3><a name="MMP">Mitochondrial membrane potential</a> (voltage sensors)</h3>
Vesa Oikonen's avatar
Vesa Oikonen committed
187

Vesa Oikonen's avatar
Vesa Oikonen committed
188
189
190
191
192
193
194
195
<p><em>Rhodamines</em> are lipophilic cations, known to accumulate in the mitochondria in proportion 
to mitochondrial membrane potential (MMP, &Delta;&Psi;m).
Several <sup>18</sup>F- and <sup>64</sup>Cu-labelled rhodamine derivatives have been synthesized, 
but the aim has been to study myocardial perfusion, and not the membrane potential 
(<a href="https://doi.org/10.1016/j.nucmedbio.2013.07.006">Bartholomä et al., 2013</a>;
<a href="https://doi.org/10.1016/j.nucmedbio.2015.06.008">Bartholomä et al., 2015</a>;
<a href="https://doi.org/10.1016/j.nucmedbio.2009.12.005">Gottumukkala et al., 2010</a>;
<a href="https://doi.org/10.1016/j.nucmedbio.2015.06.009">AlJammaz et al., 2015</a>).
Vesa Oikonen's avatar
Vesa Oikonen committed
196
MMP is high in healthy cardiomyocytes, but is decreased in ischemia.
Vesa Oikonen's avatar
Vesa Oikonen committed
197
198
199
200
201
These tracers have been used to label mitochondria in order to follow the integration of 
transplanted mitochondria in living tissue 
(<a href="https://doi.org/10.1371/journal.pone.0160889">Cowan et al., 2016</a>).
Also cancer cell lines that have high mitochondrial membrane potential can be detected with these 
tracers (<a href="https://doi.org/10.1021/mp200025m">Zhou et al., 2011</a>).
Vesa Oikonen's avatar
Vesa Oikonen committed
202
Rhodamines are substrates for P-Glycoprotein, and may therefore not be suitable
vesoik@utu.fi's avatar
vesoik@utu.fi committed
203
for imaging the brain.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
204

Vesa Oikonen's avatar
Vesa Oikonen committed
205
206
207
208
209
210
211
212
213
<p><em>Tetraphenylphosphonium</em> (TPP) cations accumulate in mitochondria driven by the negative 
potential in the matrix.
Several <sup>18</sup>F-, <sup>11</sup>C-, and <sup>64</sup>Cu-labelled TPP derivatives have been 
synthesized, mainly to measure myocardial perfusion
(<a href="https://doi.org/10.1007/s13139-016-0397-x">Kim and Min, 2016</a>;
<a href="https://doi.org/10.1016/j.ejmech.2016.04.036">Zeng et al., 2016</a>;
<a href="https://doi.org/10.1002/jlcr.3379">Tominaga et al., 2016</a>).
[<sup>18</sup>F]FBnTP has been to study the MMP in <a href="./organ_bat.html">brown adipose 
tissue</a> (<a href="https://doi.org/10.2967/jnumed.110.084657">Madar et al., 2011</a>;
vesoik@utu.fi's avatar
vesoik@utu.fi committed
214
<a href="https://doi.org/10.1371/journal.pone.0129627">Madar et al., 2015</a>).</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
215
216


vesoik@utu.fi's avatar
anchor    
vesoik@utu.fi committed
217
<h3><a name="TSPO">TSPO</a></h3>
Vesa Oikonen's avatar
Vesa Oikonen committed
218

Vesa Oikonen's avatar
Vesa Oikonen committed
219
220
221
222
<p>The <a href="./target_tspo.html">translocator protein 18kDa (TSPO)</a>, earlier called peripheral 
benzodiazepine receptor (PBR) and mitochondrial benzodiazepine receptor, is mainly situated in 
the outer mitochondrial membrane, but also in other cell organelles. 
Secretory and glandular tissues, such as <a href="./organ_adrenal_gland.html">adrenal glands</a>, 
Vesa Oikonen's avatar
Vesa Oikonen committed
223
224
225
226
227
228
pineal gland, salivary glands, and olfactory epithelium contain high levels of TSPO; intermediate 
levels in <a href="./organ_kidney.html">renal</a> and <a href="./organ_heart.html">myocardial</a> 
tissues, and low levels in <a href="./organ_brain.html">the brain</a> and 
<a href="./organ_liver.html">liver</a>. In the brain parenchyma TSPO is located in glial cells, and 
has thus been used as a biomarker of activated glial cells. It can also be found in other 
inflammatory cells. Generally, <a href="./target_tspo.html">TSPO</a> imaging might have potential in 
Vesa Oikonen's avatar
ref    
Vesa Oikonen committed
229
230
231
232
233
studying the concentration of viable mitochondria in tissues.
For instance, regional uptake of TSPO radioligand 
<a href="./analysis_11c-pbr28.html">[<sup>11</sup>C]PBR28</a> was lower in subjects with autism 
spectrum disorder in brain regions associated with sociocognitive processes
(<a href="https://doi.org/10.1038/s41380-020-0682-z">Zürcher et al., 2020</a>).</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
234
235


Vesa Oikonen's avatar
Vesa Oikonen committed
236
237
238
239
240
<h3>P2X<sub>7</sub>R</h3>

<p><a href="./target_p2-receptors.html#P2X7R">P2X<sub>7</sub> ionotropic purinoceptor</a> is 
expressed on cell membranes and also on the outer membrane of mitochondria, with its ATP-binding 
site facing the cytosol, where it can participate in regulation of oxidative phosphorylation.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
241
242
243
244
245
246
247
248


<br>
<h2>See also:</h2>

<ul>
  <li><a href="./target_apoptosis.html">Cell death</a></li>
  <li><a href="./target_hypoxia.html">Hypoxia</a></li>
Vesa Oikonen's avatar
Vesa Oikonen committed
249
  <li><a href="./ros.html">Reactive oxygen species (ROS)</a></li>
Vesa Oikonen's avatar
link    
Vesa Oikonen committed
250
  <li><a href="./organ_muscle.html">Skeletal muscle</a></li>
Vesa Oikonen's avatar
Vesa Oikonen committed
251
252
  <li><a href="./organ_bat.html">Brown adipose tissue</a></li>
  <li><a href="./target_tspo.html">Translocator protein (TSPO)</a></li>
Vesa Oikonen's avatar
Vesa Oikonen committed
253
  <li><a href="./target_fatty-acid.html">Fatty acids</a></li>
Vesa Oikonen's avatar
Vesa Oikonen committed
254
255
256
257
258
259
260
261
  <li><a href="./target_aquaporins.html#AQP8">Aquaporin-8</a></li>
</ul>


<br><hr>

<h2>References:</h2>

Vesa Oikonen's avatar
Vesa Oikonen committed
262
263
<p>Hockenbery DM (ed.): <em>Mitochondria and Cell Death</em>. Humana Press, 2016. 
doi: <a href="https://doi.org/10.1007/978-1-4939-3612-0">10.1007/978-1-4939-3612-0</a>.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
264
265
266

<p>Lionaki E, Markaki M, Palikaras K, Tavernarakis N. 
Mitochondria, autophagy and age-associated neurodegenerative diseases: 
Vesa Oikonen's avatar
Vesa Oikonen committed
267
268
new insights into a complex interplay. <em>Biochim Biophys Acta</em> 2015; 1847(11): 1412-1423. 
doi: <a href="https://doi.org/10.1016/j.bbabio.2015.04.010">10.1016/j.bbabio.2015.04.010</a>.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
269
270

<p>Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. 
Vesa Oikonen's avatar
Vesa Oikonen committed
271
272
<em>Cell</em> 2012; 148(6): 1145-1159. 
doi: <a href="https://doi.org/10.1016/j.cell.2012.02.035">10.1016/j.cell.2012.02.035</a>.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
273

Vesa Oikonen's avatar
Vesa Oikonen committed
274
275
<p>Okazawa H, Ikawa M, Tsujikawa T, Kiyono Y, Yoneda M. Brain imaging for oxidative stress and 
mitochondrial dysfunction in neurodegenerative diseases.
Vesa Oikonen's avatar
Vesa Oikonen committed
276
277
<em>Q J Nucl Med Mol Imaging</em> 2014; 58(4): 387-397.</p>

Vesa Oikonen's avatar
Vesa Oikonen committed
278
279
280
<p>Reeve AK, Simcox EM, Duchen MR, Turnbull DM (eds.): <em>Mitochondrial Dysfunction in 
Neurodegenerative Disorders</em>, 2nd ed. Springer, 2016. 
doi: <a href="https://doi.org/10.1007/978-3-319-28637-2">10.1007/978-3-319-28637-2</a>.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
281

Vesa Oikonen's avatar
Vesa Oikonen committed
282
283
<p>Santulli G (ed.): <em>Mitochondrial Dynamics in Cardiovascular Medicine</em>. Springer, 2017. 
doi: <a href="https://doi.org/10.1007/978-3-319-55330-6">10.1007/978-3-319-55330-6</a>.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
284

Vesa Oikonen's avatar
Vesa Oikonen committed
285
286
287
<p>Schaffer SW, Suleiman M (eds.): <em>Mitochondria - The Dynamic Organelle</em>.
Springer, 2007. ISBN-13: 978-0-387-69944-8.</p>

Vesa Oikonen's avatar
Vesa Oikonen committed
288
<p>Scheffler IE: <em>Mitochondria</em>, 2nd ed. Wiley, 2008. ISBN 978-0-470-04073-7.</p>
Vesa Oikonen's avatar
Vesa Oikonen committed
289
290

<br>