A Stress-Responsive Nuclear Factor, GLDI-8, Mediates Mitochondrial Stress Responses to ETC Dysfunction.

Mitochondrial electron transport chain (ETC) impairment triggers mitochondrial unfolded protein response (UPRmt) that promotes mitochondrial homeostasis, yet the nuclear factors that mediate these responses remain incompletely defined. Here, we identify GLDI-8 as a nuclear factor required for robust activation of the hsp-6p::gfp UPRmt reporter induced by ETC dysfunction in Caenorhabditis elegans. Depletion of gldi-8 markedly compromises mitochondrial stress-induced hsp-6p::gfp reporter activation, and transgenic rescue restores the response, supporting a specific requirement for GLDI-8 in this pathway. Mitochondrial stress promotes nuclear accumulation of GLDI-8; however, a GLDI-8 transcriptional (promoter) reporter shows no detectable induction under the same conditions, suggesting that regulation occurs at the post-transcriptional level. Genetic analysis further shows that stress-induced nuclear translocation of GLDI-8 is not abolished by atfs-1 knockdown, and GLDI-8 is dispensable for DVE-1 nuclear translocation under mitochondrial stress. Together, these findings establish GLDI-8 as a mitochondrial stress-responsive nuclear factor that contributes to ETC impairment-induced transcriptional responses and adds to the complex regulatory network underlying the UPRmt.