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Enhanced Levels of Peroxisome-Derived H2O2 Do Not Induce Pexophagy but Impair Autophagic Flux in HEK-293 and HeLa cells KU Leuven
Peroxisomes are functionally specialized organelles that harbor multiple hydrogen peroxide (H2O2)-producing and -degrading enzymes. Given that this oxidant functions as a major redox signaling agent, peroxisomes have the intrinsic ability to mediate and modulate H2O2-driven pro-cesses, including autophagy. However, it remains unclear whether changes in peroxisomal H2O2 (po-H2O2) emission impact the autophagic process and to which extent ...
The Mystery behind Hydrogen Peroxide Permeation across the Peroxisomal Membrane KU Leuven
As befits their name, peroxisomes play a central role in cellular hydrogen peroxide (H₂O₂) metabolism. In addition, it is increasingly appreciated that changes in peroxisomal H₂O₂ metabolism can actively contribute to the initiation and progression of redox stress-related human pathologies such as cancer, diabetes, and neurodegeneration. However, to function as a subcellular hub for H₂O₂ metabolism and signaling, peroxisomes must exchange this ...
Functional Analysis of GSTK1 in Peroxisomal Redox Homeostasis in HEK-293 Cells KU Leuven
Peroxisomes serve as important centers for cellular redox metabolism and communication. However, fundamental gaps remain in our understanding of how the peroxisomal redox equilibrium is maintained. In particular, very little is known about the function of the nonenzymatic antioxidant glutathione in the peroxisome interior and how the glutathione antioxidant system balances with peroxisomal protein thiols. So far, only one human peroxisomal ...
Identification of Peroxisome-Derived Hydrogen Peroxide-Sensitive Target Proteins by a YAP1C-based genetic probe KU Leuven
As the reversible oxidation of protein cysteine thiols is an important mechanism in signal transduction, it is essential to have access to experimental approaches that allow for spatiotemporal indexing of the cellular sulfenome in response to local changes in H2O2 levels. Here, we provide a step-by-step guide to enriching and identifying the sulfenome of mammalian cells at the subcellular level in response to peroxisome-derived H2O2 by the ...
Assessment of the Peroxisomal Redox State in Living Cells Using NADPH- and NAD+/NADH-Specific Fluorescent Protein Sensors. KU Leuven
The pyridine nucleotides NAD(H) and NADP(H) are key molecules in cellular metabolism, and measuring their levels and oxidation states with spatiotemporal precision is of great value in biomedical research. Traditional methods to assess the redox state of these metabolites are intrusive and prohibit live-cell quantifications. This obstacle was surpassed by the development of genetically encoded fluorescent biosensors enabling dynamic measurements ...
Therapeutic concentrations of calcineurin inhibitors do not deregulate glutathione redox balance in human renal proximal tubule cells KU Leuven
The calcineurin inhibitors (CNI) cyclosporine A and tacrolimus comprise the basis of immunosuppressive regimes in all solid organ transplantation. However, long-term or high exposure to CNI leads to histological and functional renal damage (CNI-associated nephrotoxicity). In the kidney, proximal tubule cells are the only cells that metabolize CNI and these cells are believed to play a central role in the origin of the toxicity for this class of ...
Peroxisomal Dysfunction and Oxidative Stress in Neurodegenerative Disease: A Bidirectional Crosstalk KU Leuven
Peroxisomes are multifunctional organelles best known for their role in cellular lipid and hydrogen peroxide metabolism. In this chapter, we review and discuss the diverse functions of this organelle in brain physiology and neurodegeneration, with a particular focus on oxida-tive stress. We first briefly summarize what is known about the vari-ous nexuses between peroxisomes, the central nervous system, oxi-dative stress, and neurodegenerative ...
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation KU Leuven
Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of ...
New mechanisms of disturbed G-protein signalling cause platelet dysfunction and impaired megakaryopoiesis KU Leuven
Heterotrimere G-eiwitten spelen een belangrijke rol in de signaaltransductie. In elk eiwit dat bij signaaltransductie betrokken is, kunnen spontane mutaties voorkomen die aanleiding geven tot een ziektebeeld bij de mens. De meerderheid van de mutaties treffen echter G-eiwit gekoppelde receptoren en de geassocieerde Ga-subeenheden, waaronder mutaties in Gsa het frequentst voorkomen. Mutaties in de coderende sequentie voor Gsa zowel als ...