Universität zu Köln

Torgovnick, Alessandro, Schiavi, Alfonso ORCID: 0000-0002-6563-8035, Shaik, Anjumara, Kassahun, Henok, Maglioni, Silvia ORCID: 0000-0001-5272-9264, Rea, Shane L., Johnson, Thomas E., Reinhardt, Hans C., Honnen, Sebastian ORCID: 0000-0002-7845-7807, Schumacher, Bjoern, Nilsen, Hilde and Ventura, Natascia (2018). BRCA1 and BARD1 mediate apoptotic resistance but not longevity upon mitochondrial stress in Caenorhabditis elegans. EMBO Rep., 19 (12). HOBOKEN: WILEY. ISSN 1469-3178

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Abstract

Interventions that promote healthy aging are typically associated with increased stress resistance. Paradoxically, reducing the activity of core biological processes such as mitochondrial or insulin metabolism promotes the expression of adaptive responses, which in turn increase animal longevity and resistance to stress. In this study, we investigated the relation between the extended Caenorhabditis elegans lifespan elicited by reduction in mitochondrial functionality and resistance to genotoxic stress. We find that reducing mitochondrial activity during development confers germline resistance to DNA damage-induced cell cycle arrest and apoptosis in a cell-non-autonomous manner. We identified the C. elegans homologs of the BRCA1/BARD1 tumor suppressor genes, brc-1/brd-1, as mediators of the anti-apoptotic effect but dispensable for lifespan extension upon mitochondrial stress. Unexpectedly, while reduced mitochondrial activity only in the soma was not sufficient to promote longevity, its reduction only in the germline or in germline-less strains still prolonged lifespan. Thus, in animals with partial reduction in mitochondrial functionality, the mechanisms activated during development to safeguard the germline against genotoxic stress are uncoupled from those required for somatic robustness and animal longevity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Torgovnick, Alessandro UNSPECIFIED UNSPECIFIED UNSPECIFIED Schiavi, Alfonso UNSPECIFIED orcid.org/0000-0002-6563-8035 UNSPECIFIED Shaik, Anjumara UNSPECIFIED UNSPECIFIED UNSPECIFIED Kassahun, Henok UNSPECIFIED UNSPECIFIED UNSPECIFIED Maglioni, Silvia UNSPECIFIED orcid.org/0000-0001-5272-9264 UNSPECIFIED Rea, Shane L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnson, Thomas E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, Hans C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Honnen, Sebastian UNSPECIFIED orcid.org/0000-0002-7845-7807 UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Nilsen, Hilde UNSPECIFIED UNSPECIFIED UNSPECIFIED Ventura, Natascia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-163635
DOI:	10.15252/embr.201845856
Journal or Publication Title:	EMBO Rep.
Volume:	19
Number:	12
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1469-3178
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIFE-SPAN EXTENSION; DNA-DAMAGE; C. ELEGANS; ELECTRON-TRANSPORT; IRON; AUTOPHAGY; METABOLISM; FRATAXIN; MUTANTS; EXTENDS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16363