Assisted Sustainability – A Practical IS Approach to Promote Corporate Sustainability

Sustainability is no longer a new trend, but an increasingly important necessity. Information Systems (IS) research is also addressing the topic more often, although, for example, company practices lack applicable solutions. At the same time, the demand for corporate sustainability and opportunities to apply digital enterprise solutions is growing. This situation creates an enormous potential to profitably couple the demand with the opportunities. In our paper, we discuss the potential that personal virtual assistants (PVAs) have to create corporate sustainability effects. Using a triangulated methodological approach, critical gaps are identified by means of a systematic literature review. Based on this, qualitative group discussions and interviews are used to analyze other influencing factors and correlations in an empirical study. It subsequently becomes clear that sustainability is subordinate to the cost-benefit trade-off, which most companies regard as being the most critical. Consequently, we present a practice-oriented bridging framework to overcome this drawback

Method development for valid high‐resolution profiling of mitochondria and Omics investigation of mitochondrial adaptions to excess energy intake and physical exercise

Dysfunctional mitochondria are widely discussed to be involved in the pathophysiology of human diseases such as cancer or diabetes. However, it is still unclear whether metabolic overflow leads to disturbances in mitochondrial substrate utilisation and, consequently, to insulin resistance or if mito-chondrial dysfunction is a consequence of impaired insulin signalling. This work aimed at elucidating this controversially discussed role of mitochondrial dysfunction in the etiology of insulin resistance and diabetes. In this context, mitochondrial adaptions to excess energy intake, insulin resistance and exercise were addressed on multiple levels using systems biological analyses of isolated mitochondria from cell culture and tissues from mouse models and humans. The applied techniques covered sample preparation, lipidomics approaches and also protein and functional analyses including enzymatic assays and high-resolution respirometry. Changes in lipid homeostasis are very likely to affect mitochondrial membrane composition which, in turn, regulates mitochondrial structure and function. Since most lipids are not specific for individual organelles and therefore challenging to quantify in cell or tissue lysates in a mitochondria-specific fashion, an accurate, comprehensive lipid profiling strategy which first enriches mitochondria and minimises contaminations by membranes from other organelles was established and published in the context of this thesis as a prerequisite to investigate the contribution of individual lipids to mitochondrial (dys-)function (Kappler et al. (2016)130). Mitochondria isolation by ultracentrifugation yielded the purest samples and was used for further lipidomics analyses of mitochondria obtained from cell culture models and mouse tissues in this thesis. The two other methods tested in this work, differential centrifugation and an antibody coupled-magnetic bead assisted method, revealed more contaminations from other organelles. Therefore, they may result in misleading conclusions when isolating only impure mitochondria for ”omics” analyses. The established lipidomics approach was further modified by adding the antioxidant butylated hydroxytoluene for analyses of a special class of oxidised lipids, the oxysterols. To study the hypothesis that skeletal muscle insulin resistance is the primary defect that is evident decades before β-cell failure and hyperglycemia develops, isolated mitochondria of a murine skeletal muscle cell line were investigated after induction of insulin resistance by chronic hyperinsulinemia and in the absence or presence of high glucose conditions. In this thesis it is shown, that chronic high glucose and insulin stimulation led to a decrease of mitochondrial mass in the C2C12 myotubes. This could be caused by the lower reliance on oxidative phosphorylation for ATP generation supported by the observed lower oxidative respiratory capacity. This hypothesis is further underlined by a concomitant switch in electron transport chain substrate preference. Hence, the cell culture findings of this thesis support the hypothesis that insulin resistance can be the cause of decreased or incomplete mitochondrial oxidation leading to metabolite accumulation, further impairing insulin signalling. Additionally, this thesis reveals that both hyperinsulinemia and glucose oversupply caused decreased superoxide dismutase (SOD) activity and SOD 1 protein abundance on a mitochondria-specific level, since it was observed solely in isolated mitochondria, but not whole cell lysates. Mitochondria are the major sites for reactive oxygen species (ROS) production and increasing evidence suggests that oxidative stress plays a major role in the pathogenesis of type 2 diabetes mellitus. The observed change in antioxidative defence and its impact on ROS levels are an interesting finding worthwhile to be further investigated. To gain further comprehensive understanding of the molecular changes underlying the alterations in mitochondrial function and metabolic control induced by an energy-rich western diet and additionally to unravel the mechanisms by which exercise compensates overnutrition and prevents mitochondrial dysfunction, a high energy diet feeding mouse experiment including regular treadmill exercise training with subsequent lipidomics and functional investigations was employed. Whereas the higher fatty acid oxidation capacity observed under high-energy feeding was concomitant with an increased mitochondrial mass in skeletal muscle, this was not observed in liver. A higher mitochondrial oxidative capacity in high-energy-fed mice could be due to a compensatory increased mitochondrial function in insulin resistance to overcome excess substrate supply. The fact that this is mainly observed in skeletal muscles of animal models, makes it a probable rodent-specific phenomenon and therefore relevance for humans remains inconclusive. Muscle oxidative capacity was affected by both diet and training, while liver was solely and greatly affected by diet. Although function of muscle and liver mitochondria was affected differently by training and high-energy diet feeding, diet had a much greater impact on the lipid composition of the mitochondria in both tissues than training. The highly tissue-specific lipid compositions of muscle and liver mitochondria, as shown in this thesis, were affected similarly facing the high-energy diet. Training adaptions on lipid level seem to be rather subtle. Quantitative proteomics analyses, that are currently performed might further elucidate tissue-specific mitochondrial adaptations and a tissue-specific contribution to disease pathologies. Notably, mitochondrial fatty acid composition of the detected lipid classes did not always reflect the dietary fatty acid composition. This points to a selective process for lipid incorporation into mitochondria. Besides differences in the adaptation to diet and exercise, the comparison of liver and muscle mito-chondria revealed clear differences in lipid composition, enzyme abundance and respiration. Contrary to muscle, isolated hepatic mitochondria did not show an increase in respiration after adding pyruvate as an additional substrate to fatty acids. This detected “non-response” to pyruvate in respiration of isolated liver, but not muscle mitochondria supports the hypothesis of mitochondria being tailored to specific tissue demands. When fatty acids are already present, the findings of this thesis suggest that externally provided pyruvate is directly shuttled into anabolic processes such as gluconeogenesis or ketogenesis. Pyruvate is thus not used for ATP production via oxidative phosphorylation. In contrast, in muscle mitochondria, pyruvate can be used for oxidative phosphorylation even in the presence of fatty acids to react to the great changes in energy demand in this tissue for example during exercise. This was not only supported by a higher protein abundance of electron transport chain complexes and in general a higher mitochondrial mass, but also by a higher amount of lipids like cardiolipins and phosphatidylethanolamines, all associated with a higher electron transport chain activity, respiration and supercomplex assembly. Investigations on mitochondrial specificities of liver and skeletal muscle as two insulin target organs, responsible for endogenous glucose production and disposal, could help to elucidate the tissue-specific role in health (e.g. exercise) and disease and might lead to more target-specific treatments of mitochondrial dysfunctions associated with for example insulin resistance and type 2 diabetes. A further broadening of the knowledge about the mitochondrial role in development and prevention of type 2 diabetes is needed. A special focus should be on ruling out the controversy of published data, probably also caused by many different functional approaches applied in the studies all referring to the broad and general term “mitochondrial function”. This may be achieved by highly comparable and standardised experiments (e.g. suitable surrogate markers for mitochondrial mass) taking into account species and tissue specific mitochondrial differences. The methodology developed in this thesis can form a basis for future standardisation.Mitochondriale Dysfunktion wird wegen ihrer zentralen Rolle im Stoffwechsel oft in Zusammenhang mit der Pathophysiologie von humanen Krankheiten wie zum Beispiel Diabetes und Krebs gebracht. Es ist jedoch noch ungeklärt, ob eine erhöhte Energieaufnahme und damit Angebot an Metaboliten zu einer gestörten mitochondrialen Substratoxidation mit resultierender Insulinresistenz führt, oder ob eine mitochondriale Dysfunktion Folge einer gestörten Insulinsignalkaskade ist. Das Ziel dieser Arbeit war die kontroverse Rolle der mitochondrialen Dysfunktion in der Ätiologie von Insulinresistenz und Diabetes zu untersuchen. Zu diesem Zweck wurden mitochondriale Veränderungen infolge von überschüssiger Energieaufnahme, Insulinresistenz und Sport mittels systembiologischer Analysen in isolierten Mitochondrien aus Zellkultur, murinen und humanen Geweben untersucht. Die angewendeten Techniken umfassten die Probenvorbereitung, Lipidomics-Analysen, aber auch Protein- und Funktionsanalysen sowie enzymatische Tests und hochauflösende Atmungsmessungen. Veränderungen in der Lipidhomeostase beeinflussen sehr wahrscheinlich die Zusammensetzung der mitochondrialen Membranen mit Folgen für die Mitochondrienstruktur und -funktion. Da die meisten Lipide nicht spezifisch für einzelne Zellorganellen sind, ist es eine Herausforderung, Mitochondrien-spezifische Lipide in Zell- oder Gewebelysaten zu quantifizieren. Um den Beitrag einzelner Lipide zur mitochondrialen Funktion/Dysfunktion untersuchen zu können wurde eine präzise und umfassende Methode zur Analyse von Mitochondrien-spezifischen Lipiden als Teil dieser Doktorarbeit etabliert und bereits publiziert (Kappler et al. (2016)130).Die Isolierung von Mitochondrien mittels Ultrazentrifugation führte zur besten Aufreinigung und wurde daher für die Lipidanalysen von Mitochondrien aus Zellkultur und Gewebe in dieser Doktorarbeit verwendet. Zur Mitochondrienisolation wurden auch die differentielle Zentrifugation und ein Ansatz basierend auf Beads mit gekoppeltem Antikörper in dieser Doktorarbeit getestet. Beide Methoden führten zu mehr Verunreinigungen mit anderen Organellen und die Aufreinigung von unreinen Mitochondrien könnte daher möglicherweise eine Missinterpretation von Ergebnissen in OMICS-Analysen nach sich ziehen. Die etablierte Methode zur Lipidanalyse wurde durch die Zugabe von dem antioxidativen butyliertem Hydroxytoluen modifiziert, um oxidierte Lipide, die sogenannten Oxysterole analysieren zu können. Basierend auf der Hypothese, dass sich die Insulinresistenz im Skelettmuskel schon Jahrzehnte vor dem β-Zellversagen und der Hyperglykämie manifestiert, wurden Mitochondrien einer murinen Skelettmuskelzelllinie nach Induktion von Insulinresistenz mit chronischer Hyperinsulinämie in der An- oder Abwesenheit von Hyperglykämie isoliert und untersucht. In dieser Doktorarbeit konnte gezeigt werden, dass chronisch hohe Glukose- und Insulinkonzentrationen zu einer erniedrigten Mitochondrienmasse in C2C12 Myotuben führten. Dies könnte durch eine geringere Abhängigkeit der Zellen von der oxidativen Phosphorylierung zur ATP Produktion bedingt sein. Dafür spricht auch die ebenfalls beobachtete verringerte oxidative Kapazität und eine geänderte Substratpräferenz der Elektronentranportkette. Somit unterstützen die Ergebnisse dieser Doktorarbeit die Hypothese, dass Insulinresistenz zu einer verminderten oder inkompletten mitochondriale Oxidation führen könnte, wodurch Metabolite akkumulieren, die die Insulinsignalkaskade weiter beeinträchtigen. Zusätzlich konnte in dieser Doktorarbeit gezeigt werden, dass sowohl Hyperinsulinämie als auch ein Überangebot an Glukose eine reduzierte Superoxid Dismutase (SOD) Enzymaktivität und SOD1 Proteinabundanz ausschließlich in Mitochondrien hervorrufen, da diese Veränderungen nur in isolierten Mitochondrien nicht jedoch im Gesamtzelllysat beobachtet wurden. Mitochondrien sind die Hauptquelle für die Bildung von Sauerstoffradikalen (ROS) und es gibt zunehmend Hinweise, dass oxidativer Stress eine wichtige Rolle in der Pathogenese des Typ 2 Diabetes spielt. Die beobachteten Veränderungen in der antioxidativen Abwehr und deren Auswirkungen auf die ROS Level sind ein interessanter Befund und werden weiter untersucht. Um ein umfassenderes Verständnis für die molekularen Veränderungen der Mitochondrien durch funktionelle und metabolische Adaptionen an eine Hoch-Energie-Diät und Ausdauertraining zu erlangen wurde ein Mausexperiment durchgeführt. Zusätzlich wurden Lipidomics und funktionelle Analysen durchgeführt, um die Mechanismen von Ausdauertraining aufzuklären, welche die Folgen von Überernährung kompensieren und eine mitochondriale Dysfunktion verhindern. Hoch-Energie-Diät erhöhte nicht nur die Fettsäureoxidation im Muskel, sondern auch die Mitochondrienmenge. Dies wurde in der Leber nicht beobachtet. Die erhöhte oxidative Kapazität unter Hoch-Energie-Diät könnte einen Kompensationsmechanismus der Mitochondrien darstellen, um dem Überangebot an Substraten in der Insulinresistenz entgegenzuwirken. Die Tatsache, dass dies hauptsächlich im Skelettmuskel von Tiermodellen beobachtet wurde legt die Vermutung nahe, dass es sich hierbei um ein spezifisches Phänomen im Nager handeln könnte und die Relevanz für den Menschen daher fraglich ist. Die oxidative Kapazität im Muskel wurde durch Diät und Training beeinflusst, wohingegen in Leber nur ein Einfluss der Diät zu beobachten war. Obwohl die Funktion von Mitochondrien aus Muskel und Lebergewebe durch Training und Hoch-Energie-Diät unterschiedlich beeinflusst wurde, hatte die Diät einen bedeutend größeren Einfluss auf die Lipidkomposition der Mitochondrien in beiden Geweben. In dieser Doktorarbeit konnte gezeigt werden, dass die Lipidzusammensetzung von Mitochondrien in Muskel und Leber äußerst Gewebe-spezifisch ist, aber in ähnlicher Weise durch die Hoch-Energie-Diät beeinflusst wurde. Die Effekte von Ausdauertraining auf Lipide der Mitochondrien scheinen eher gering zu sein. Quantitative Proteomanalysen, die momentan durchgeführt werden, könnten helfen die gewebespezifischen mitochondriellen Adaptionen und ihren Beitrag zur Krankheitsentwicklung aufzuklären. Bemerkenswerterweise spiegelte die mitochondriale Fettsäurezusammensetzung in den de-tektieren Lipidklassen nicht immer die Fettsäurezusammensetzung der Diäten wieder. Dies deutet darauf hin, dass die Lipidaufnahme in Mitochondrien ein selektiver Prozess ist. Abgesehen von einer unterschiedlichen Adaption an Diät und Training, zeigte der Vergleich von Leber- und Muskelmitochondrien auch klare Unterschiede in der Lipidzusammensetzung, Enzyma-bundanz und mitochondrialer Respiration. Im Gegensatz zu isolierten Mitochondrien aus Muskel, zeigten Mitochondrien aus Leber keinen Anstieg in der Respiration nach Zugabe von Pyruvat als zusätzliches Atmungskettensubstrat neben Fettsäuren. Dieses Nichtansprechen von isolierten Lebermitochondrien, aber nicht von Muskelmitochondrien, auf Pyruvat in Atmungsmessungen, unterstützt die Hypothese, dass Mitochondrien auf die Ansprüche des jeweiligen Gewebes zugeschnitten und angepasst sind. Die Ergebnisse dieser Doktorarbeit deuten darauf hin, dass wenn Fettsäuren bereits anwesend sind, extern zugeführtes Pyruvat in Lebermitochondrien direkt in anabole Prozesse wie Gluconeogenese oder Ketogenese überführt wird und daher nicht zur ATP Produktion über die oxidative Phosphorylierung verwendet wird. In Muskelmitochondrien hingegen, wird Pyruvat selbst in der Anwesenheit von Fettsäuren der oxidativen Phosphorylierung zugeführt, um die großen Schwankungen im Energiebedarf des Muskels zum Beispiel bei Sport erfüllen zu können. Die Hypothese wird weiter unterstützt durch eine höhere Abundanz der Elektronentransportkettenproteine, einer generell höheren Menge an Mitochondrien und auch durch eine höhere Menge an Lipiden wie Cardiolipin und Phosphatidylenthanolamin, die mit einer höheren Elektronentransportkettenaktivität, Atmung und Superkomplexbildung assoziiert werden. Untersuchungen bezüglich der Spezifitäten von Mitochondrien aus insulinempfindlichen Organen wie Skelettmuskel und Lebe, welche für die endogene Glukoseproduktion und –abbau verantwortlich sind, könnten dabei helfen eine gewebespezifische Rolle der Mitochondrien bei zum Beispiel Sport und Krankheiten zu ermitteln. Dies könnte zu einer mehr zielgerichteten Behandlung von mitochondrialer Dysfunktion führen, welche im Zusammenhang mit Insulinresistenz und Diabetes diskutiert wird. Die Beteiligung von Mitochondrien an der Entwicklung und Prävention von Typ 2 Diabetes muss noch weiter untersucht werden. Hierbei sollte ein besonderer Fokus darauf liegen, die kontroverse Datenlage bereits publizierter Studien zu klären. Diese beruht wahrscheinlich teilweise darauf, dass unter dem sehr breiten und allgemeinen Begriff der „Mitochondrienfunktion“ diverse verschiedene experimentelle Ansätze angewendet und publiziert werden. Eine Standardisierung der Experimente unter Einbeziehung von Speziesunterschieden und Gewebeunterschieden wie auch die Einführung von vereinheitlichten Parametern wie zum Beispiel zur Quantifizierung von Mitochondrien könnten helfen. Die Methodik welche in dieser Doktorarbeit entwickelt wurde kann zur weiteren Standardisierung beitragen

Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease

Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4+ T cells specific for these ligands in all HLA-DP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4+ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD

Beryllium-specific CD4+ T cells induced by chemokine neoantigens perpetuate inflammation

Discovering dominant epitopes for T cells, particularly CD4+ T cells, in human immune-mediated diseases remains a significant challenge. Here, we used bronchoalveolar lavage (BAL) cells from HLA-DP2-expressing patients with chronic beryllium disease (CBD), a debilitating granulomatous lung disorder characterized by accumulations of beryllium (Be)-specific CD4+ T cells in the lung. We discovered lung resident CD4+ T cells that expressed a disease-specific public CDR3β T cell receptor motif and were specific to Be-modified self-peptides derived from C-C motif ligands 4 (CCL4) and 3 (CCL3). HLA-DP2-CCL/Be tetramer staining confirmed that these chemokine-derived peptides represented major antigenic targets in CBD. Furthermore, Be induced CCL3 and 4 secretion in the lungs of mice and humans. In a murine model of CBD, the addition of LPS to Be oxide exposure enhanced CCL4 and CCL3 secretion in the lung and significantly increased the number and percentage of CD4+ T cells specific for the HLA-DP2-CCL/Be epitope. Thus, we demonstrate a direct link between Be-induced innate production of chemokines and the development of a robust adaptive immune response to those same chemokines presented as Be-modified self-peptides, creating a vicious cycle of innate and adaptive immune activation

Beryllium-specific CD4\u3csup\u3e+\u3c/sup\u3e T cells induced by chemokine neoantigens perpetuate inflammation

Discovering dominant epitopes for T cells, particularly CD4+ T cells, in human immune-mediated diseases remains a significant challenge. Here, we used bronchoalveolar lavage (BAL) cells from HLA-DP2–expressing patients with chronic beryllium disease (CBD), a debilitating granulomatous lung disorder characterized by accumulations of beryllium-specific (Be-specific) CD4+ T cells in the lung. We discovered lung-resident CD4+ T cells that expressed a disease-specific public CDR3β T cell receptor motif and were specific to Be-modified self-peptides derived from C-C motif ligand 4 (CCL4) and CCL3. HLADP2–CCL/Be tetramer staining confirmed that these chemokine-derived peptides represented major antigenic targets in CBD. Furthermore, Be induced CCL3 and CCL4 secretion in the lungs of mice and humans. In a murine model of CBD, the addition of LPS to Be oxide exposure enhanced CCL4 and CCL3 secretion in the lung and significantly increased the number and percentage of CD4+ T cells specific for the HLA-DP2–CCL/Be epitope. Thus, we demonstrate a direct link between Be-induced innate production of chemokines and the development of a robust adaptive immune response to those same chemokines presented as Be-modified self-peptides, creating a cycle of innate and adaptive immune activation

Hidden politics of power and governmentality in transitional justice and peacebuilding:The problem of ‘bringing the local back in’

This paper examines ‘the local’ in peacebuilding by examining how ‘local’ transitional justice projects can become spaces of power inequalities. The paper argues that focusing on how ‘the local’ contests or interacts with ‘the international’ in peacebuilding and post-conflict contexts obscures contestations and power relations amongst different local actors, and how inequalities and power asymmetries can be entrenched and reproduced through internationally funded local projects. The paper argues that externally funded projects aimed at emancipating ‘locals’ entrench inequalities and create local elites that become complicit in governing the conduct and participation of other less empowered ‘locals’. The paper thus proposes that specific local actors—often those in charge of externally funded peacebuilding projects—should also be conceptualised as governing agents: able to discipline and regulate other local actors’ voices and their agency, and thus (re)construct ideas about what ‘the local’ is, or is not

Extracellular matrix hydrogels from decellularized tissues: structure and function

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discusse

Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease

Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4(+) T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4(+) T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4(+) T cells specific for these ligands in all HLA-DP2(+) CBD patients tested. Thus, our findings identify the first ligand for a CD4(+) T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of 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 contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of 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 contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery