Spatial and temporal control of mitochondrial H 2 O 2 release in intact human cells.

Autor: Hoehne MN; Department for Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, Cologne, Germany., Jacobs LJHC; Department for Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, Cologne, Germany., Lapacz KJ; Department for Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, Cologne, Germany., Calabrese G; Department for Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, Cologne, Germany., Murschall LM; Department for Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, Cologne, Germany., Marker T; Department for Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, Cologne, Germany., Kaul H; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany., Trifunovic A; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.; Center for Molecular Medicine, University of Cologne, Cologne, Germany., Morgan B; Institute of Biochemistry, Centre for Human and Molecular Biology (ZHMB), Saarland University, Saarbruecken, Germany., Fricker M; Department of Plant Sciences, University of Oxford, Oxford, UK., Belousov VV; Department of Metabolism and Redox Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russia.; Federal Center of Brain Research and Neurotechnologies, FMBA, Moscow, Russia.; Institute for Cardiovascular Physiology, Georg August University Göttingen, Göttingen, Germany., Riemer J; Department for Chemistry, Institute for Biochemistry, Redox Biochemistry, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2022 Apr 04; Vol. 41 (7), pp. e109169. Date of Electronic Publication: 2022 Feb 11.
DOI: 10.15252/embj.2021109169
Abstrakt: Hydrogen peroxide (H 2 O 2 ) has key signaling roles at physiological levels, while causing molecular damage at elevated concentrations. H 2 O 2 production by mitochondria is implicated in regulating processes inside and outside these organelles. However, it remains unclear whether and how mitochondria in intact cells release H 2 O 2 . Here, we employed a genetically encoded high-affinity H 2 O 2 sensor, HyPer7, in mammalian tissue culture cells to investigate different modes of mitochondrial H 2 O 2 release. We found substantial heterogeneity of HyPer7 dynamics between individual cells. We further observed mitochondria-released H 2 O 2 directly at the surface of the organelle and in the bulk cytosol, but not in the nucleus or at the plasma membrane, pointing to steep gradients emanating from mitochondria. Gradient formation is controlled by cytosolic peroxiredoxins, which act redundantly and with a substantial reserve capacity. Dynamic adaptation of cytosolic thioredoxin reductase levels during metabolic changes results in improved H 2 O 2 handling and explains previously observed differences between cell types. Our data suggest that H 2 O 2 -mediated signaling is initiated only in close proximity to mitochondria and under specific metabolic conditions.
(© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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