Universität zu Köln

Hermeling, Johannes CW (2022). Deciphering the redox signalling pathway in long-lived mitochondrial mutant. PhD thesis, Universität zu Köln.

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Abstract

Most manipulations that extend lifespan also increase cytoprotective mechanisms to various stress in a range of animals from yeast to mammals. However, the underlying signalling cascades regulating stress resistance and longevity are still largely unknown. Here, we identified a mitochondrial ROS (mtROS) pulse during L4 as novel activator of transcriptional factor Krüppel-like factor-1 in isp-1(150);ctb-1(189) mitomutant. For this purpose, we created a de novo outer mitochondrial membrane (OMM) H2O2 sensor by adding a TOMM20 targeting sequence to the roGFP2-Orp1 probe. We further show that H2O2 signalling is dependent on superoxide dismutase-1 (SOD-1), peroxiredoxin-3 (PRDX-3) and voltage-dependent anion channel-1 (VDAC- 1). Upon the ROS signal, KLF-1 is activated by the p38 MAPK signalling cascade and translocates to the nucleus where it activates genes involved in phase I of xenobiotic detoxification programme, the cytochrome P450 oxidases (CYPs). Collectively, these findings underline the importance of ROS, especially H2O2, as signalling molecule and identify the p38 MAPK signalling cascade as a key regulator of mitomutant lifespan.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Hermeling, Johannes CW mat.hermeling@gmail.com UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-647487
Date:	2022
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects:	Natural sciences and mathematics Life sciences
Uncontrolled Keywords:	Keywords Language Redox signalling English Mitochondria English Ageing English
Date of oral exam:	21 January 2022
Referee:	Name Academic Title Trifunovic, Aleksandra Prof. Dr. Vilchez, David Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/64748