Reproductive regulation of the mitochondrial stress response in Caenorhabditis elegans
Nikolaos Charmpilas, Aggeliki Sotiriou, Konstantinos Axarlis, Nektarios Tavernarakis, Thorsten Hoppe
Abstract
Proteome integrity is fundamental for cellular and organismal homeostasis. The mitochondrial unfolded protein response (UPR mt ), 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 UPR mt inducibility under physiological conditions remains elusive. Here, we show that an intact germline is essential for robust UPR mt induction in the Caenorhabditis elegans somatic tissues. A series of nematode mutants with germline defects are unable to respond to genetic or chemical UPR mt inducers. Our genetic analysis suggests that reproductive signals, rather than germline stem cells, are responsible for somatic UPR mt induction. Consistent with this observation, we show that UPR mt 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 UPR mt decline.