Universität zu Köln

Hoehne, Michaela Nicole, Jacobs, Lianne J. H. C., Lapacz, Kim Jasmin ORCID: 0000-0002-2494-4124, Calabrese, Gaetano ORCID: 0000-0002-2212-5280, Murschall, Lena Maria, Marker, Teresa, Kaul, Harshita, Trifunovic, Aleksandra ORCID: 0000-0002-5472-3517, Morgan, Bruce ORCID: 0000-0001-9393-1071, Fricker, Mark ORCID: 0000-0002-8942-6897, Belousov, Vsevolod V. and Riemer, Jan ORCID: 0000-0002-7574-8457 (2022). Spatial and temporal control of mitochondrial H2O2 release in intact human cells. Embo J., 41 (7). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

Hydrogen peroxide (H2O2) has key signaling roles at physiological levels, while causing molecular damage at elevated concentrations. H2O2 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 H2O2. Here, we employed a genetically encoded high-affinity H2O2 sensor, HyPer7, in mammalian tissue culture cells to investigate different modes of mitochondrial H2O2 release. We found substantial heterogeneity of HyPer7 dynamics between individual cells. We further observed mitochondria-released H2O2 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 H2O2 handling and explains previously observed differences between cell types. Our data suggest that H2O2-mediated signaling is initiated only in close proximity to mitochondria and under specific metabolic conditions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoehne, Michaela Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Jacobs, Lianne J. H. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lapacz, Kim Jasmin UNSPECIFIED orcid.org/0000-0002-2494-4124 UNSPECIFIED Calabrese, Gaetano UNSPECIFIED orcid.org/0000-0002-2212-5280 UNSPECIFIED Murschall, Lena Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Marker, Teresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaul, Harshita UNSPECIFIED UNSPECIFIED UNSPECIFIED Trifunovic, Aleksandra UNSPECIFIED orcid.org/0000-0002-5472-3517 UNSPECIFIED Morgan, Bruce UNSPECIFIED orcid.org/0000-0001-9393-1071 UNSPECIFIED Fricker, Mark UNSPECIFIED orcid.org/0000-0002-8942-6897 UNSPECIFIED Belousov, Vsevolod V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemer, Jan UNSPECIFIED orcid.org/0000-0002-7574-8457 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-688857
DOI:	10.15252/embj.2021109169
Journal or Publication Title:	Embo J.
Volume:	41
Number:	7
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1460-2075
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HYDROGEN-PEROXIDE; SUPEROXIDE-PRODUCTION; 2-CYS PEROXIREDOXINS; MAMMALIAN-CELLS; MECHANISMS; ROS; SPECIFICITY; GENERATION; SITES Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68885