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) | ||||||||
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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 |
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Date of oral exam: | 21 January 2022 | ||||||||
Referee: |
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Refereed: | Yes | ||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/64748 |
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