Reproductive regulation of the mitochondrial stress response in Caenorhabditis elegans
Nikolaos Charmpilas,
Aggeliki Sotiriou,
Konstantinos Axarlis,
Nektarios Tavernarakis,
Thorsten Hoppe
Affiliations
Nikolaos Charmpilas
Institute for Genetics, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Aggeliki Sotiriou
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece; Division of Basic Sciences, School of Medicine, University of Crete, Heraklion, Greece
Konstantinos Axarlis
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece
Nektarios Tavernarakis
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece; Division of Basic Sciences, School of Medicine, University of Crete, Heraklion, Greece; Corresponding author
Thorsten Hoppe
Institute for Genetics, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital of Cologne, Cologne, Germany; Corresponding author
Summary: Proteome integrity is fundamental for cellular and organismal homeostasis. The mitochondrial unfolded protein response (UPRmt), a key component of the proteostasis network, is activated in a non-cell-autonomous manner in response to mitochondrial stress in distal tissues. However, the importance of inter-tissue communication for UPRmt inducibility under physiological conditions remains elusive. Here, we show that an intact germline is essential for robust UPRmt induction in the Caenorhabditis elegans somatic tissues. A series of nematode mutants with germline defects are unable to respond to genetic or chemical UPRmt inducers. Our genetic analysis suggests that reproductive signals, rather than germline stem cells, are responsible for somatic UPRmt induction. Consistent with this observation, we show that UPRmt is sexually dimorphic, as male nematodes are inherently unresponsive to mitochondrial stress. Our findings highlight a paradigm of germline-somatic communication and suggest that reproductive cessation is a primary cause of age-related UPRmt decline.
