Reproductive regulation of the mitochondrial stress response in Caenorhabditis elegans

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.

Keywords: C. elegans; CP: Developmental biology; CP: Molecular biology; aging; germline; mitochondria; proteostasis; unfolded protein response.