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The mitochondrial energy conversion involves cytochrome c diffusion into the respiratory supercomplexes
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Kinetics of integrated electron transfer in the mitochondrial respiratory chain: random collisions versus solid state electron channelling
No full textThe Interplay Between Respiratory Supercomplexes and ROS in Aging
Full text linkSignificance: The molecular mechanism of aging is still vigorously debated, although a general consensus
exists that mitochondria are significantly involved in this process. However, the previously postulated role of
mitochondrial-derived reactive oxygen species (ROS) as the damaging agents inducing functional loss in aging
has fallen out of favor in the recent past. In this review, we critically examine the role of ROS in aging in the
light of recent advances on the relationship between mitochondrial structure and function. Recent Advances:
The functional mitochondrial respiratory chain is now recognized as a reflection of the dynamic association of
respiratory complexes in the form of supercomplexes (SCs). Besides providing kinetic advantage (channeling),
SCs control ROS generation by the respiratory chain, thus providing a means to regulate ROS levels in the cell.
Depending on their concentration, these ROS are either physiological signals essential for the life of the cell or
toxic species that damage cell structure and functions. Critical Issues: We propose that under physiological
conditions the dynamic nature of SCs reversibly controls the generation of ROS as signals involved in mitochondrial-
nuclear communication. During aging, there is a progressive loss of control of ROS generation so that
their production is irreversibly enhanced, inducing a vicious circle in which signaling is altered and structural
damage takes place. Future Directions: A better understanding on the forces affecting SC association would
allow the manipulation of ROS generation, directing these species to their physiological signaling role
Coenzyme Q Function in Mitochondria
No full textIn this chapter we provide a review with a focus on the function of
Coenzyme Q (CoQ, ubiquinone) in mitochondria. The notion of a mobile pool of
CoQ in the lipid bilayer as the vehicle of electrons from respiratory complexes has
somewhat changed with the discovery of respiratory supramolecular units, in particular
the supercomplex comprising Complexes I and III; in such assembly the
electron transfer is thought to be mediated by direct channelling, and we provide
evidence for a kinetic advantage on the transfer based on random collisions. The
CoQ pool, however, has a fundamental function in establishing a dissociation equilibrium
with bound CoQ, besides being required for electron transfer from other
dehydrogenases to Complex III. CoQ bound to Complex I and to Complex III is also
involved in proton translocation; although the mechanism of the Q-cycle is well
established for Complex III, the involvement of CoQ in proton translocation by
Complex I is still debated. This review also briefly examines some additional roles
of CoQ, such as the antioxidant effect of its reduced form and its postulated action
at the transcriptional level
Chapter 5. Mitochondrial Supercomplexes and ROS Regulation: Implications for Ageing
No full textCONTENTS
5.1 Introduction
5.2 Respiratory Supercomplexes: Structure and Function
5.2.1 Molecular Composition
5.2.2 Dynamic Nature and Kinetic Advantage of Supercomplexes
5.3 ROS Generation by Mitochondria
5.3.1 Respiratory Chain as a Source of ROS
5.3.1.1 Complex I
5.3.1.2 Complex III
5.3.1.3 Other Respiratory Enzymes
5.4 Mitochondrial ROS as Signals: Targets and Mechanisms
5.5 Regulation of Mitochondrial ROS Generation
5.5.1 Role of Mitochondrial Membrane Potential
5.5.2 Role of Post-Translational Modifications
5.5.3 Hypoxia and ROS Production
5.5.4 Role of Supercomplexes
5.6 ROS and Mitochondrial Quality Control
5.7 Implications for Ageing
5.7.1 Unifying Hypothesis Involving Supercomplex Destabilization in Agein
Coenzyme Q and respiratory supercomplexes: physiological and pathological implications
No full textIt was discovered over 60 years ago that the mitochondrial respiratory chain is constituted of a series of protein complexes imbedded in the inner mitochondrial membrane. Experimental evidence has more recently ascertained that the major respiratory complexes involved in energy conservation are assembled as supramolecular units (supercomplexes, SCs) in stoichiometric ratios. The functional role of SCs is less well defined, and still open to discussion. Several lines of evidence favour the concept that electron transfer from Complex I to Complex III operates by channelling of electrons through Coenzyme Q molecules bound to the SC I1III2IVn, in contrast with the previously accepted hypothesis that the transfer of reducing equivalents from Complex I to Complex III occurs via random diffusion of the Coenzyme Q molecules in the lipid bilayer. On the contrary, electron transfer from Complex III to Complex IV seems to operate, at least in mammals, by random diffusion of cytochrome c molecules between the respiratory complexes even if assembled in SCs. Furthermore, another property provided by the supercomplex assembly is the control of generation of reactive oxygen species by Complex I, that might be important in the regulation of signal transduction from mitochondria. This review discusses physiological and pathological implications of the supercomplex assembly of the respiratory chain
Two separate pathways underlie NADH and succinate oxidation in swine heart mitochondria: Kinetic evidence on the mobile electron carriers
Full text link: We have investigated NADH and succinate aerobic oxidation in frozen and thawed swine heart mitochondria. Simultaneous oxidation of NADH and succinate showed complete additivity under a variety of experimental conditions, suggesting that the electron fluxes originating from NADH and succinate are completely independent and do not mix at the level of the so-called mobile diffusible components. We ascribe the results to mixing of the fluxes at the level of cytochrome c in bovine mitochondria: the Complex IV flux control coefficient in NADH oxidation was high in swine mitochondria but very low in bovine mitochondria, suggesting a stronger interaction of cytochrome c with the supercomplex in the former. This was not the case in succinate oxidation, in which Complex IV exerted little control also in swine mitochondria. We interpret the data in swine mitochondria as restriction of the NADH flux by channelling within the I-III2-IV supercomplex, whereas the flux from succinate shows pool mixing for both Coenzyme Q and probably cytochrome c. The difference between the two types of mitochondria may be ascribed to different lipid composition affecting the cytochrome c binding properties, as suggested by breaks in Arrhenius plots of Complex IV activity occurring at higher temperatures in bovine mitochondria
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