The mitochondrial unfolded protein response (mitoUPR) is a stress response pathway that promotes cell survival and restores mitochondrial function when mitochondrial health is compromised (Haynes et al. 2013; Jovaisaite et al. 2014; Shpilka and Haynes 2018). While a mitoUPR was first reported in mammalian cells (Zhao et al. 2002), the initial work on the mitoUPR in C. elegans was performed by Yoneda et al. who found that treatment with ethidium bromide, which affects the replication and expression of mitochondrial DNA, increased the expression of the mitochondrial chaperone gene
hsp-6 (Yoneda et al. 2004). Based on this observation, they generated
hsp-6p::gfp and
hsp-60p::gfp reporter strains to further study the mitoUPR. They found that either RNA interference (RNAi) targeting
spg-7, the worm homolog of paraplegin, or RNAi targeting other genes encoding mitochondrial proteins resulted in activation of the
hsp-6p::gfp and
hsp-60p::gfp reporter strains (Yoneda et al. 2004).