RRC ID 59417
Author Torgovnick A, Schiavi A, Shaik A, Kassahun H, Maglioni S, Rea SL, Johnson TE, Reinhardt HC, Honnen S, Schumacher B, Nilsen H, Ventura N.
Title BRCA1 and BARD1 mediate apoptotic resistance but not longevity upon mitochondrial stress in Caenorhabditis elegans.
Journal EMBO Rep
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.
Volume 19(12)
Published 2018-12-1
DOI 10.15252/embr.201845856
PII embr.201845856
PMID 30366941
PMC PMC6280797
MeSH Animals Apoptosis* Caenorhabditis elegans / cytology* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Cell Proliferation DNA Damage DNA Repair Germ Cells / cytology Longevity* Mitochondria / metabolism* Mitosis Stress, Physiological* Tumor Suppressor Proteins / metabolism* Ubiquitin-Protein Ligases / metabolism*
IF 8.383
Times Cited 0
C.elegans tm1145 tm853