Biomedical Engineering Reference
In-Depth Information
across the membrane and down their concentration gradient through ATP synthase
that uses stored energy. Within the inner mitochondrial membrane, the lipid-soluble
electron carrier coenzyme-Q10 carries both electrons and protons from its oxidized
ubiquinone form (UQ; a.k.a. quinone Q) to its reduced ubiquinol form (UQH
2
or QH
2
). In the coenzyme-Q10 redox cycle, oxidized ubiquinone UQ accepts
2 electrons and 2 protons, whereas reduced ubiquinol UQH
2
releases 2 electrons
and 2 protons.
The electron transport chain is composed of 4 major complexes: NADH-
ubiquinone reductase (complex-I), succinate-ubiquinone reductase (complex-II),
ubiquinol-cytochrome-C reductase (complex-III), and cytochrome-C oxidase
(complex-IV). Electron transfer between these complexes is ensured by interactions
between electron carriers coenzyme-Q10 and cytochrome-C.
Cardiolipin can link complex-III and -IV. In addition, complex-I is stabilized
by binding to complex-III in human mitochondria. Like complex-I, -III, and -IV
(but not complex-II), ATP synthase (complex-V) is able to form supercomplexes by
oligomerization [
344
]. A dimeric state of ATP synthase is specific for mitochondria.
Respirasomes
refers to respiratory chain supercomplexes such as the aggregate
made by complex-I, -III dimer, and -IV (respirasome-I-III-IV). These supercom-
plexes reduce electron diffusion distance.
5.2.3.3
PGC1
'
and PGC1
“
Peroxisome
proliferator-activated
receptor-
γ
(or
nuclear
receptor
NR1c3)
coactivators PGC1
α
and PGC1
β
are highly expressed in the heart. The expression
of PGC1
rises when ATP production must increase, i.e., when the cardiac
activity increases. Regulator PGC1
α
α
coactivates PPAR
α
(nuclear receptor NR1c1),
estrogen-related receptor ERR
(NR3b1), and other nuclear factors that control the
transcription of genes involved in cardiac fatty acid oxidation and mitochondrial
functional capacity [
345
].
Moreover, PGC1
α
stimulates the mitochondrial genesis in cardiomyocytes,
although it is not essential for mitochondrial generation. In the absence of PGC1
α
,
mitochondrial density remains normal, but expression of the genes of oxidative
phosphorylation decays [
346
]. Homeostasis of ATP and phosphocreatine is dis-
turbed. The Gs-coupled
α
AR-cAMP pathway, calmodulin-binding catalytic subunit
of PP3, calcium-calmodulin-dependent protein kinase, AMP-activated protein ki-
nase, P38MAPK, and nitric oxide activates PGC1
β
α
expression.
5.2.3.4
Mitochondrial Permeability Transition Pore
Mitochondrial permeability transition pore (mPTP) is a non-selective, large-
conductance channel that remains normally closed. It is partly constituted of:
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