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As the knowledge base and importance of mitochondrial physiology to human health expand, the necessity for harmonizing nomenclature concerning mitochondrial respiratory states and rates has become increasingly apparent. Clarity of concept and consistency of nomenclature are key trademarks of a research field. These trademarks facilitate effective transdisciplinary communication, education, and ultimately further discovery. Peter Mitchell’s chemiosmotic theory establishes the link between vectorial and scalar energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theory and nomenclature for mitochondrial physiology and bioenergetics. Herein, we follow IUPAC guidelines on general terms of physical chemistry, extended by considerations on open systems and irreversible thermodynamics. We align the nomenclature and symbols of classical bioenergetics with a concept-driven constructive terminology to express the meaning of each quantity clearly and consistently. In this position statement, in the frame of COST Action MitoEAGLE, we endeavour to provide a balanced view on mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately support the development of databases of mitochondrial respiratory function in species, tissues, and cells.

A limited number of cases, estimated in just 5-10 over 100, of breast cancer are caused by hereditary genetic mutations. When this happens, even a single mutation of a gene (BRCA1 or BRCA2) contributes to a high likelihood of developing breast cancer, also during young adulthood. Women diagnosed with genetic mutations face numerous psychosocial challenges managing their cancer risk, communicating the genetic diagnosis to family members, and disclosing their status to current or potential partners. The idiographic approach is a promising strategy to understand the challenging nature of these situations, because of its ability to investigate meanings and implications of complex phenomena. In particular, it contributes to the identification of elements that guide the psychological support to the client, especially around the communication process and the potential prophylactic surgery. Aim of the present chapter is therefore to illustrate the case study of a young woman with breast cancer related to a BRCA2 mutation. Through the review of the psychological consultation with her, it will be possible to present some clinically relevant suggestions about the work with this group of women and to reflect on the resources associated with the use of the idiographic approach.

The function of uncoupling protein 3 is still not established. Mitochondrial uncoupling, control of ROS production, protection against lipotoxicity and protection against oxidative stress are functions classically discussed. To establish a role for uncoupling protein 3 in these functions, we have here used uncoupling protein 3 (-/-) mice, backcrossed for 10 generations on a C57Bl/6 background. In isolated skeletal muscle mitochondria, we examined uncoupled respiration, both unstimulated and in the presence of fatty acids. We did not observe any difference between mitochondria from wildtype and uncoupling protein 3(-/-) mice. We measured H(2)O(2) production rate and respiration rate under reactive oxygen species-generating conditions (succinate without rotenone) but found no effect of uncoupling protein 3. We tested two models of acute lipotoxicity-fatty acid-induced oxidative inhibition and fatty acid-induced swelling-but did not observe any protective effect of uncoupling protein 3. We examined oxidative stress by quantifying 4-hydroxynonenal protein adducts and protein carbonyls in the mitochondria-but did not observe any protective effect of uncoupling protein 3. We conclude that under the experimental conditions tested here, we find no evidence for the function of uncoupling protein 3 being basal or induced uncoupling, regulation of ROS production, protection against acute lipotoxicity or protection against oxidative damage.

Mice lacking the thermogenic mitochondrial membrane protein UCP1 (uncoupling protein 1) - and thus all heat production from brown adipose tissue - can still adapt to a cold environment (4 degrees C) if successively transferred to the cold. The mechanism behind this adaptation has not been clarified. To examine possible adaptive processes in the skeletal muscle, we isolated mitochondria from the hind limb muscles of cold-acclimated wild-type and UCP1(-/-) mice and examined their bioenergetic chracteristics. We observed a switch in metabolism, from carbohydrate towards lipid catabolism, and an increased total mitochondrial complement, with an increased total ATP production capacity. The UCP1(-/-) muscle mitochondria did not display a changed state-4 respiration rate (no uncoupling) and were less sensitive to the uncoupling effect of fatty acids than the wild-type mitochondria. The content of UCP3 was increased 3-4 fold, but despite this, endogenous superoxide could not invoke a higher proton leak, and the small inhibitory effect of GDP was unaltered, indicating that it was not mediated by UCP3. Double mutant mice (UCP1(-/-) plus superoxide dismutase 2-overexpression) were not more cold sensitive than UCP1(-/-), bringing into question an involvement of reactive oxygen species (ROS) in activation of any alternative thermogenic mechanism. We conclude that there is no evidence for an involvement of UCP3 in basal, fatty-acid- or superoxide-stimulated oxygen consumption or in GDP sensitivity. The adaptations observed did not imply any direct alternative process for nonshivering thermogenesis but the adaptations observed would be congruent with adaptation to chronically enhanced muscle activity caused by incessant shivering in these mice.

Contains fulltext : 81777.pdf (publisher's version ) (Closed access), The mtDNA mutator mice have high levels of point mutations and linear deletions of mtDNA causing a progressive respiratory chain dysfunction and a premature aging phenotype. We have now performed molecular analyses to determine the mechanism whereby these mtDNA mutations impair respiratory chain function. We report that mitochondrial protein synthesis is unimpaired in mtDNA mutator mice consistent with the observed minor alterations of steady-state levels of mitochondrial transcripts. These findings refute recent claims that circular mtDNA molecules with large deletions are driving the premature aging phenotype. We further show that the stability of several respiratory chain complexes is severely impaired despite normal synthesis of the corresponding mtDNA-encoded subunits. Our findings reveal a mechanism for induction of aging phenotypes by demonstrating a causative role for amino acid substitutions in mtDNA-encoded respiratory chain subunits, which, in turn, leads to decreased stability of the respiratory chain complexes and respiratory chain deficiency.

Part of urn:nbn:se:su:diva-549