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Mitochondrial Redox Regulation in Adaptation to Exercise
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Christopher P. Hedges, Troy L. Merry
Skeletal muscle contraction requires energy in the form of ATP. Almost all types of exercise will require mitochondrial oxidative phosphorylation (OXPHOS) to supply at least a portion of the ATP used. Production of ATP by mitochondria is dependent on the electron transport system and oxidative phosphorylation machinery. In brief, complexes I and II, mitochondrial glycerophosphate dehydrogenase (mGPDH) and electron transferring flavoprotein dehydrogenase (ETFDH) all reduce the lipophilic mobile electron carrier ubiquinone to ubiquinol. Ubiquinol is then oxidised by complex III, which reduces cytochrome c, which is, in turn, oxidised by complex IV. Complex IV utilises electrons to bind and reduce oxygen and protons (H+) to form water (H2O). During this process, each time an electron transitions down energy states the released energy is used by complexes I, III and IV to transport H+ into the intermembrane space which is against the H+ concentration gradient (Schultz and Chan, 2001). The net result is the generation of a proton motive force, made up of a concentration gradient of H+ and an electrochemical membrane potential across the mitochondrial inner membrane. Proton motive force enables production of ATP by ATP synthase (mitochondrial complex V) simultaneous with H+ return to the mitochondrial matrix (Fillingame, 1997). Thus, ATP production is coupled to oxygen consumption in the mitochondria.
Role of Tandem Mass Spectrometry in Diagnosis and Management of Inborn Errors of Metabolism
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Kannan Vaidyanathan, Sandhya Gopalakrishnan
The levels of expression of mitochondrial matrix proteins including isovaleryl coenzyme A dehydrogenase, agmatinase, and cytochrome b5 were downregulated in early stages of Wilson’s disease. As mitochondrial injuries progressed, expression levels of malate dehydrogenase 1, annexin A5, S-adenosylhomocysteine hydrolase, transferrin, and sulfite oxidase 1 were differentially regulated. S-adenosylhomocysteine hydrolase was under-expressed and is hypothesized to play a role in neurological pathology of Wilson’s disease. The study was done on a mouse model of Wilson’s disease (LEC rats) [57]. Shotgun proteomic analysis of Atp7b(-/-) mouse model of Wilson’s disease revealed increased expression of DNA repair machinery and nucleus-localized glutathione peroxidase (SeIH), and reduced expression ofligand-activated nuclear receptors FXR/NR1H4 and GR/NR3C1 and nuclear receptor-interacting partners [58]. Remodeling of RNA processing machinery may be involved in the pathogenesis of Wilson’s disease [59].
Ultrastructural Abnormalities of the Heart During Diabetes
Published in Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla, Heart Dysfunction in Diabetes, 2019
Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla
Mitochondrial abnormalities are the most common ultrastructural disturbance reported in the heart during diabetes. Examples of some of these abnormalities are presented in the electron micrographs of Figures 8 and 9. Mitochondrial swelling is most frequently observed13,22,23,37,38,40 although one study reported mitochondrial shrinkage.21 Generalized mitochondrial disruption15 is evident in the form of vacuolization of the mitochondria,25 clearing of the matrix,13,25 separated cristae,22 and lysis of both inner and outer mitochondrial membranes.25 This damage may be a result of increased lysosomal activity in hearts from diabetic animals. An incorporation of lysosomal membranes into the mitochondrial matrix has been observed.13 An increase in the number of electron-dense particles in the mitochondria has also been reported.21,23 This may reflect an accumulation of Ca2+ ions.
Passive heat stress induces mitochondrial adaptations in skeletal muscle
Published in International Journal of Hyperthermia, 2023
Erik D. Marchant, W. Bradley Nelson, Robert D. Hyldahl, Jayson R. Gifford, Chad R. Hancock
Aside from the apparent role of HSP72 in activating PGC-1α through AMPK and SIRT1, heat shock proteins play a vital role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix, as well as in helping fold and assemble them into complexes [52]. The mitochondrial proteome is composed of over 1,000 proteins, 99% of which are nuclear encoded, with only 13 being coded for by mitochondrial DNA [80]. Because most mitochondrial proteins are translated outside the mitochondria, specialized import machinery is required to introduce newly synthesized proteins into the mitochondrial matrix. Two primary players in this process are the translocase of the outer membrane (TOM), and the translocase of the inner membrane (TIM) [81]. Interestingly, both cytosolic and mitochondrial heat shock proteins are vital for this translocation process, partially due to their interactions with TIM and TOM [81–83]. Furthermore, once introduced into the mitochondria, heat shock protein 60 is necessary for the proper folding and assembly of the respiratory complexes of the electron transport system [84]. To date, it is unknown if passive heating in humans or animals improves protein import and folding due to increased HSP content or activation in skeletal muscle. However, the vital role of HSPs in mitochondrial protein import and assembly suggests that this is an important area for future research.
Pharmacotherapeutic options for cancer cachexia: emerging drugs and recent approvals
Published in Expert Opinion on Pharmacotherapy, 2023
Lorena Garcia-Castillo, Giacomo Rubini, Paola Costelli
Carnitine and creatine have been used as supplements for decades in athletic populations to enhance physical performance. L-Carnitine is an amino acid derivative, especially found in both skeletal and cardiac muscles. It is involved in the transport of long-chain fatty acids from the cytosol into the mitochondrial matrix for β-oxidation. L-Carnitine deficiency could lead to an inefficient bioenergetic function promoting oxidative stress and the release of pro-inflammatory cytokines [26]. In this regard, a double-blind trial performed several years ago assessed the effectiveness of L-carnitine supplementation on advanced pancreatic cancer patients. Although the sample size was rather small to reach statistical power, the results were encouraging, showing improvement of body weight and body composition [27]. Oral supplementation with creatine has also been shown to enhance both muscle strength and lean body mass (LBM). Creatine can be endogenously synthesized and is mainly stored and used in the skeletal muscle, especially to provide a rapid energy source for muscle contraction. In addition, creatine is endowed with antioxidant properties and prevents the increase of circulating pro-inflammatory cytokines [26].
Nutritional and dietary aspects in polycystic ovary syndrome: insights into the biology of nutritional interventions
Published in Gynecological Endocrinology, 2020
Luísa Pinheiro Pimenta Neves, Rodrigo Rodrigues Marcondes, Giovana De Nardo Maffazioli, Ricardo Santos Simões, Gustavo Arantes Rosa Maciel, Jose Maria Soares, Edmund Chada Baracat
A substance that is also drawing researchers’ attention is carnitine. It is most important in the transportation of long-chain fatty acids to the mitochondrial matrix where it becomes available for β-oxidation to enable energy production. Since all enzymes aiding β-oxidation are located within the mitochondria, tissues require a necessary amount of carnitine for the energy production process to take place [28]. The carnitine system seems to have a role in insulin regulation [29]. A study carried out by Fenkci et al. [30] analyzed serum total L-carnitine levels in nonobese women with PCOS and compared them with those of the control group. They found that the women with PCOS had a significantly reduced level of total L-carnitine in comparison with the healthy group, but no correlation with insulin resistance was found. Vigerust et al. [31] found a slight tendency toward reduction in the free carnitine level; however, it was not sufficient to support the aforementioned result.