A5081662652- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Metabolism, Diabetes, and Cancer
- Photoreceptor and optogenetics research
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- Nitric Oxide and Endothelin Effects
- Analytical Chemistry and Sensors
- Ion Transport and Channel Regulation
- Molecular Sensors and Ion Detection
- Metabolism and Genetic Disorders
- Potassium and Related Disorders
- Autophagy in Disease and Therapy
- Advanced biosensing and bioanalysis techniques
- Adipose Tissue and Metabolism
- Cardiac electrophysiology and arrhythmias
- Glycosylation and Glycoproteins Research
- Cellular transport and secretion
- Neuroscience and Neural Engineering
- Cancer-related gene regulation
- Neural dynamics and brain function
Medical University of Graz
2016-2025
University of Tübingen
2020-2024
Changes in intra- and extracellular potassium ion (K+) concentrations control many important cellular processes related biological functions. However, our current understanding of the spatiotemporal patterns physiological pathological K+ changes is severely limited by lack practicable detection methods. We developed K+-sensitive genetically encoded, Förster resonance energy transfer-(FRET) based probes, called GEPIIs, which enable quantitative real-time imaging dynamics. GEPIIs as purified...
Reprogramming of metabolic pathways determines cell functions and fate. In our work, we have used organelle-targeted ATP biosensors to evaluate cellular settings with high resolution in real time. Our data indicate that mitochondria dynamically supply for glucose phosphorylation a variety cancer types. This hexokinase-dependent process seems be reversed upon the removal or other hexose sugars. further verify cells increased consumption. Similar subcellular fluxes occurred young mouse...
Distinct subcellular pH levels, especially in lysosomes and endosomes, are essential for the degradation, modification, sorting, accumulation, secretion of macromolecules. Here, we engineered a novel genetically encoded probe by fusing pH-stable cyan fluorescent protein (FP) variant, mTurquoise2, to highly pH-sensitive enhanced yellow protein, EYFP. This approach yielded ratiometric biosensor—referred as pH-Lemon—optimized live imaging distinct conditions within acidic cellular compartments....
Recently identified core proteins (MICU1, MCU, EMRE) forming the mitochondrial Ca
Abstract Nitric oxide ("Equation missing"<!-- image only, no MathML or LaTex -->) is a free radical with wide range of biological effects, but practically impossible to visualize in single cells. Here we report the development novel multicoloured fluorescent quenching-based "Equation --> probes by fusing bacteria-derived -->-binding domain close distinct protein variants. These genetically encoded probes, referred as geNOps, provide selective, specific and real-time read-out cellular...
The endoplasmic reticulum (ER) imports ATP and uses energy from hydrolysis for protein folding trafficking. However, little is known about how this vital transport occurs across the ER membrane. Here, using three commonly used cell lines (CHO, INS1 HeLa), we report that enters lumen through a cytosolic Ca2+-antagonized mechanism, or CaATiER (Ca2+-Antagonized Transport into ER). Significantly, show mitochondria supply to SERCA-dependent Ca2+ gradient membrane necessary ER, SLC35B1/AXER. We...
Control of Ca 2+ flow from the ER to mitochondria by calnexin balances output energy production pathways.
Cancer represents a leading cause of death worldwide. Hence, better understanding the molecular mechanisms causing and propelling disease is utmost importance. Several cancer entities are associated with altered K+ channel expression which frequently decisive for malignancy outcome. The impact such oncogenic channels on cell patho-/physiology homeostasis their roles in different subcellular compartments is, however, far from being understood. A refined method to simultaneously investigate...
Abstract Aims Na+-activated Slack potassium (K+) channels are increasingly recognized as regulators of neuronal activity, yet little is known about their role in the cardiovascular system. activity increases when intracellular Na+ concentration ([Na+]i) reaches pathophysiological levels. Elevated [Na+]i a major determinant ischaemia and reperfusion (I/R)-induced myocardial injury; thus, we hypothesized that plays under these conditions. Methods results K+ currents cardiomyocytes (CMs)...
Cameleons are sophisticated genetically encoded fluorescent probes that allow quantifying cellular Ca2+ signals. The based on Förster resonance energy transfer (FRET) between terminally located proteins (FPs), which move together upon binding of to the central calmodulin myosin light chain kinase M13 domain. Most available cameleons consist cyan and yellow FPs (CFP YFP) as FRET pair. However, red-shifted versions with green orange or red (GFP, OFP, RFP) have some advantages such less...
Mitochondrial Ca2+ uptake regulates diverse endothelial cell functions and has also been related to nitric oxide (NO•) production. However, it is not entirely clear if the organelles support or counteract NO• biosynthesis by taking up Ca2+. The objective of this study was verify whether mitochondrial influences Ca2+-triggered generation synthase (eNOS) in an immortalized line (EA.hy926), respective primary human umbilical vein cells (HUVECs) eNOS-RFP (red fluorescent protein) expressing...
Mitochondrial sirtuins (Sirts) control important cellular processes related to stress. Despite their regulatory importance, however, the dynamics and subcellular distributions of Sirts remain debatable. Here, we investigate localization sirtuin 4 (Sirt4), a variant with mitochondrial targeting sequence (MTS), by expressing Sirt4 fused superfolder green fluorescent protein (Sirt4-sfGFP) in HeLa pancreatic β-cells. Super resolution fluorescence microscopy revealed trapping Sirt4-sfGFP outer...
The neuronal Na+-activated K+ channel Slack (aka Slo2.2, KNa1.1, or Kcnt1) has been implicated in setting and maintaining the resting membrane potential defining excitability firing patterns, as well generation of slow afterhyperpolarization following bursts action potentials. activity increases significantly under conditions high intracellular Na+ levels, suggesting this may exert important pathophysiological functions. To address these putative roles, we studied whether channels contribute...
Abstract Ca 2+ -activated K + channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, whether mechanistically how activity interferes with metabolic energy consumption rates, which fundamental for rapidly growing cells. Using cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis mitochondrial ATP-production reduced derived...
The members of the nitric oxide synthase (NOS) family, eNOS, nNOS and iNOS, are well-characterized enzymes. However, due to lack suitable direct NO sensors, little is known about kinetic properties cellular generation by different isoenzymes. Very recently, we developed a novel class fluorescent protein-based NO-probes, geNOps, which allow real-time measurement fluctuation. By applying these genetic biosensors nNOS-, eNOS- iNOS-expressing HEK293 cells were able characterize respective...
High expression levels of mitochondria-associated hexokinase-II (HKII) represent a hallmark metabolically highly active cells such as fast proliferating cancer cells. Typically, the enzyme provides crucial metabolic switch towards aerobic glycolysis. By imaging activities on single-cell level with genetically encoded fluorescent biosensors, we here demonstrate that HKII activity requires intracellular K+. The K+ dependency glycolysis in expressing was confirmed cell populations using...
Nongenetic optical control of neurons is a powerful technique to study and manipulate the function nervous system. This research has benchmarked performance organic electrolytic photocapacitor (OEPC) optoelectronic stimulators at level single mammalian cells: human embryonic kidney (HEK) cells with heterologously expressed voltage-gated K
Given the importance of ion gradients and fluxes in biology, monitoring ions locally at exterior plasma membrane intact cells a noninvasive manner is highly desirable but challenging. Classical targeting genetically encoded biosensors cell surfaces would be suitable approach; however, it often leads to intracellular accumulation tools vesicular structures adverse modifications, possibly impairing sensor functionality. To tackle these issues, we generated recombinant fluorescent fused...