Universität zu Köln

Hermeling, Johannes C. W., Herholz, Marija, Baumann, Linda, Cores, Estela Cepeda, Zecic, Aleksandra, Hoppe, Thorsten, Riemer, Jan and Trifunovic, Aleksandra ORCID: 0000-0002-5472-3517 (2022). Mitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans. Redox Biol., 58. AMSTERDAM: ELSEVIER. ISSN 2213-2317

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Abstract

Alternations of redox metabolism have been associated with the extension of lifespan in roundworm Caenorhabditis elegans, caused by moderate mitochondrial dysfunction, although the underlying signalling cascades are largely unknown. Previously, we identified transcriptional factor Kruppel-like factor-1 (KLF-1) as the main regulator of cytoprotective longevity-assurance pathways in the C. elegans long-lived mitochondrial mutants. Here, we show that KLF-1 translocation to the nucleus and the activation of the signalling cascade is dependent on the mitochondria-derived hydrogen peroxide (H2O2) produced during late developmental phases where aerobic respiration and somatic mitochondrial biogenesis peak. We further show that mitochondrial-inducible superoxide dismutase-3 (SOD-3), together with voltage-dependent anion channel-1 (VDAC-1), is required for the life-promoting H(2)O(2 )signalling that is further regulated by peroxiredoxin-3 (PRDX-3). Increased H2O2 release in the cytoplasm activates the p38 MAPK signalling cascade that induces KLF-1 translocation to the nucleus and the activation of transcription of C. elegans longevity-promoting genes, including cytoprotective cytochrome P450 oxidases. Taken together, our results underline the importance of redox-regulated signalling as the key regulator of longevity-inducing pathways in C. elegans, and position precisely timed mitochondria-derived H2O2 in the middle of it.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hermeling, Johannes C. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herholz, Marija UNSPECIFIED UNSPECIFIED UNSPECIFIED Baumann, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Cores, Estela Cepeda UNSPECIFIED UNSPECIFIED UNSPECIFIED Zecic, Aleksandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemer, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Trifunovic, Aleksandra UNSPECIFIED orcid.org/0000-0002-5472-3517 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-664957
DOI:	10.1016/j.redox.2022.102533
Journal or Publication Title:	Redox Biol.
Volume:	58
Date:	2022
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2213-2317
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language KRUPPEL-LIKE FACTOR; LIFE-SPAN EXTENSION; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; C. ELEGANS; SUPEROXIDE-PRODUCTION; MOLECULAR-MECHANISM; DYSFUNCTION; METABOLISM; INHIBITOR Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66495