Erich Gnaiger

Erich Gnaiger
Medizinische Universität Innsbruck · Daniel Swarovski Forschungslabor

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271
Publications
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11,753
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Publications

Publications (271)
Article
Full-text available
The oxidation of proline to pyrroline-5-carboxylate (P5C) leads to the transfer of electrons to ubiquinone in mitochondria that express proline dehydrogenase (ProDH). This electron transfer supports Complexes CIII and CIV, thus generating the protonmotive force. Further catabolism of P5C forms glutamate, which fuels the citric acid cycle that yield...
Article
Full-text available
Iron is an essential component for metabolic processes, including oxygen transport within hemoglobin, tricarboxylic acid (TCA) cycle activity, and mitochondrial energy transformation. Iron deficiency can thus lead to metabolic dysfunction and eventually result in iron deficiency anemia (IDA), which affects approximately 1.5 billion people worldwide...
Article
Full-text available
Measurement of oxygen consumption of cultured cells is widely used for diagnosis of mitochondrial diseases, drug testing, biotechnology, and toxicology. Fibroblasts are cultured in monolayers, but physiological measurements are carried out in suspended or attached cells. We address the question whether respiration differs in attached versus suspend...
Article
Full-text available
Multiple non-aggregatory functions of human platelets (PLT) are widely acknowledged, yet their functional examination is limited mainly due to a lack of standardized isolation and analytic methods. Platelet apheresis (PA) is an established clinical method for PLT isolation aiming at the treatment of bleeding diathesis in severe thrombocytopenia. On...
Article
Full-text available
Iron is an essential co-factor for many cellular metabolic processes, and mitochondria are main sites of utilization. Iron accumulation promotes production of reactive oxygen species (ROS) via the catalytic activity of iron species. Herein, we investigated the consequences of dietary and genetic iron overload on mitochondrial function. C57BL/6N wil...
Article
Full-text available
Redox states of the mitochondrial coenzyme Q pool, which reacts with the electron transfer system, reflect the balance between (1) reducing capacities of electron flow from fuel substrates converging at the Q-junction, (2) oxidative capacities downstream of Q to O2, and (3) the load on the OXPHOS system utilizing or dissipating the protonmotive for...
Article
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Human blood cells may offer a minimally invasive strategy to study systemic alterations of mitochondrial function. Here we tested the reliability of a protocol designed to study mitochondrial respiratory control in human platelets (PLTs) in field studies, using high-resolution respirometry (HRR). Several factors may trigger PLT aggregation during t...
Article
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The identification of novel physiological regulators that stimulate energy expenditure through brown adipose tissue (BAT) activity in substrate catalysis is of utmost importance to understand and treat metabolic diseases. Myoglobin (MB), known to store or transport oxygen in heart and skeletal muscles, has recently been found to bind fatty acids wi...
Article
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The molecular assembly of cells depends not only on the balance between anabolism and catabolism, but to a large degree on the building blocks available in the environment. For cultured mammalian cells, this is largely determined by the composition of the applied growth medium. Here we study the impact of lipids in the medium on mitochondrial membr...
Article
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Tumor cells display metabolic alterations when compared to non-transformed cells. These characteristics are crucial for tumor development, maintenance and survival providing energy supplies and molecular precursors. Anaplerosis is the property of replenishing the TCA cycle, the hub of carbon metabolism, participating in the biosynthesis of precurso...
Article
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Only a few studies have evaluated changes in mitochondrial function and oxidative stress associated with ultramarathon running. Invasive biopsies are needed to assess mitochondrial function of skeletal muscle, which may not be well tolerated by some individuals. Platelets (PLTs) as a metabolically highly active and homogenous cell population were s...
Article
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Rewiring of energy metabolism and adaptation of mitochondria are considered to impact on prostate cancer development and progression. Here, we report on mitochondrial respiration, DNA mutations and gene expression in paired benign/malignant human prostate tissue samples. Results reveal reduced respiratory capacities with NADH-pathway substrates glu...
Article
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Ultramarathon running represents a major physical challenge even for elite athletes. Runners wellbeing may be challenged by fluid and electrolyte disturbances, hemolysis and skeletal muscle damage, decline in hepatic function and kidney injury. We hypothesized that these effects may even be exacerbated in non-elite runners. Physiological, hematolog...
Preprint
Full-text available
As the knowledge base and importance of mitochondrial physiology to human health 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 unif...
Preprint
Full-text available
As the knowledge base and importance of mitochondrial physiology to human health 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 unif...
Article
Full-text available
Abstract: As the knowledge base and importance of mitochondrial physiology to human health 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...
Article
Full-text available
Background Myofascial trigger points (MTrPs) are hyperirritable areas in the fascia of the affected muscle, possibly related to mitochondrial impairment. They can result in pain and hypoxic areas within the muscle. This pilot study established a minimally invasive biopsy technique to obtain high-quality MTrP tissue samples to evaluate mitochondrial...
Article
Background: Restless legs syndrome is a sensorimotor neurological disorder of the limbs that impairs quality of life and disturbs sleep. However, there has been progress in understanding the disease involving the dopaminergic system as well as iron metabolism. The exact pathophysiological mechanisms of restless legs syndrome remain elusive. We trie...
Article
Full-text available
Epilepsies are a group of common neurological diseases exerting a strong burden on patients and society, often lacking clear etiology and effective therapeutical strategies. Early intervention during the development of epilepsy (epileptogenesis) is of great medical interest, though hampered by poorly characterized epileptogenetic processes. Using t...
Data
(Related to Figures 4, 5). mRNA levels of selected subunits of respiratory complexes of WT and enkephalin deficient mice (KO), normalized to beta-actin and basal levels of untreated animals are depicted: NDUFs3 (A,D), SDHb (B,E), and ATP6 (C,F). Data from (A–C) have been obtained from the hippocampus of the hemisphere of injection, data from (D–F)...
Data
(Related to Figure 3). Numbers of somatostatin immuno-positive neurons were analyzed from WT and Enk-/- mice (KO) in the hippocampal subfields at different time-intervals after KA. Almost complete cell loss was observed ipsilaterally (A,C,E). Somatostatin positive neurons were mostly conserved contralaterally (B,D,F). No genotype specific differenc...
Data
(Related to Figures 1–3). Enkephalin (Enk) protein- and mRNA-levels during epileptogenesis are depicted. Images in (A) represent contralateral hippocampi stained for pro-Enk (pEnk) or mature Enk (Enk) after saline or kainic acid (KA) injection at different time intervals. mRNA-levels in the dentate gyrus of WT mice for dynorphin (B), neuropeptide Y...
Data
(Related to Figure 2). mRNA-levels of opioid receptors in WT and Enk-/- mice (KO) and additional data on cell numbers are depicted. mRNA levels were assessed for delta-, mu-, and kappa-opioid receptors (DOPr, MOPr, KOPr, respectively) in the hippocampus and cortex of young adult male mice (A–F). Nissl-stained hippocampal sections 1 week (1w) and 2...
Preprint
Full-text available
As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theoryestablishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unify...
Preprint
Full-text available
In view of the broad implications for health care, mitochondrial researchers face an 121 increasing responsibility to disseminate their fundamental knowledge and novel discoveries to 122 a wide range of stakeholders and scientists beyond the group of specialists. This requires 123 implementation of a commonly accepted terminology within the discipl...
Article
Full-text available
The idea of using metabolic aberrations as targets for diagnosis or therapeutic intervention has recently gained increasing interest. In a previous study, our group discovered intriguing differences in the oxidative mitochondrial respiration capacity of benign and prostate cancer (PCa) cells. In particular, we found that PCa cells had a higher tota...
Chapter
Protocols for High-Resolution FluoRespirometry of intact cells, permeabilized cells, permeabilized muscle fibers, isolated mitochondria, and tissue homogenates offer sensitive diagnostic tests of integrated mitochondrial function using standard cell culture techniques, small needle biopsies of muscle, and mitochondrial preparation methods. Multiple...
Chapter
High-Resolution FluoRespirometry is a well-established and versatile approach to study mitochondrial oxygen uptake amperometrically in combination with measurement of fluorescence signals. One of the most frequently applied fluorescent dyes is Amplex UltraRed for monitoring rates of hydrogen peroxide production. Selection of an appropriate mitochon...
Article
This study aimed to investigate and compare the effects of repeated-sprint (RSH) and sprint interval training in hypoxia (SIH) on sea level running and cycling performance, and to elucidate potential common or divergent adaptations of muscle perfusion and -oxygenation as well as mitochondrial respiration of blood cells. Eleven team-sport athletes p...
Article
Full-text available
Current strategies used to quantitatively describe the biological diversity of lipids by mass spectrometry are often limited in assessing the exact structural variability of individual molecular species in detail. A major challenge is represented by the extensive isobaric overlap present among lipids, hampering their accurate identification. This i...
Article
Full-text available
Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from...
Chapter
Respirometric analysis of mitochondrial function in human immune cells and platelets has become increasingly attractive, since such tests can be accomplished within a few hours and may thereby support early diagnosis of diseases with mitochondrial dysfunctions. Here we discuss methodological aspects of blood cell preparation, show examples of measu...
Article
Iron is an essential co-factor for several metabolic processes, including mitochondrial respiration, and mitochondria are the major sites of iron-utilization. Cellular iron homeostasis must be tightly regulated, as intracellular iron deficiency can lead to insufficient energy production, whereas iron overload triggers ROS (reactive oxygen species)...
Conference Paper
During the past three decades, measurement of mitochondrial oxygen (O2) consumption during respiratory steady-states and at higher-than-physiological O2 concentrations has become a gold standard not only in mitochondrial biochemistry but in a wide range of health sciences as well [1]. In contrast, kinetic aspects, such as O2 dependence of mitochond...
Preprint
Full-text available
Intracellular signaling pathways not only control cell proliferation and survival, but also regulate the provision of cellular energy and building blocks through mitochondrial and non-mitochondrial metabolism. Wild-type and oncogenic RAF kinases have been shown to prevent apoptosis following the removal of interleukin 3 (IL-3) from mouse pro-myeloi...
Article
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The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison with Lowlander populations, have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e. metabolic ad...
Article
Full-text available
Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated biases, we studied mitochondrial respiratory control in permea...
Data
Oxygen consumption values for individual subjects and samples reported in this study. (XLSX)
Article
Full-text available
At the annual Iditarod Race, Alaskan Huskies repeatedly run for up to 8 hours at 16 km/h to complete 1600 km. We previously demonstrated high rates of mitochondrial protein synthesis in Alaskan Huskies, which we suspected allowed rapid remodeling of mitochondrial proteins in response to energetic stress. The purpose of this study was to examine mit...
Preprint
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The capacity of mitochondrial oxidative phosphorylation (OXPHOS) and fuel substrate supply are key determinants of cardiac muscle performance. Although temperature exerts a strong effect on energy metabolism, until recently numerous respiratory studies of mammalian mitochondria have been carried out below physiological temperature, with substrates...
Article
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In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the con...
Conference Paper
Investigating mitochondrial responses to hypoxia may reveal plasticity of cellular bioenergetics relevant to the study of environmental adaptation and chronic disease. The present study evaluated the bioenergetic phenotype of vastus lateralis muscle biopsies from 15 subjects at sea level and following 16 d at 5200 m by high resolution respirometry...
Article
Full-text available
Altered mitochondrial metabolism plays a pivotal role in the development and progression of various diseases, including cancer. Cell lines are frequently used as models to study mitochondrial (dys)function but little is known about their mitochondrial respiration and metabolic properties in comparison to the primary tissue of origin. We have develo...
Article
We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male...
Article
Full-text available
During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western...