A tRNA processing enzyme is a key regulator of the mitochondrial unfolded protein response.

ABSTRACT: The mitochondrial unfolded protein response (UPR^mt) has emerged as a predominant mechanism that preserves mitochondrial function. Consequently, multiple pathways likely exist to modulate UPR^mt. We discovered that the tRNA processing enzyme, homolog of ELAC2 (HOE-1), is key to UPR^mt regulation in Caenorhabditis elegans. We find that nuclear HOE-1 is necessary and sufficient to robustly activate UPR^mt. We show that HOE-1 acts via transcription factors ATFS-1 and DVE-1 that are crucial for UPR^mt. Mechanistically, we show that HOE-1 likely mediates its effects via tRNAs, as blocking tRNA export prevents HOE-1-induced UPR^mt. Interestingly, we find that HOE-1 does not act via the integrated stress response, which can be act

SUBMITTER: Held JP 

PROVIDER: S-EPMC9064297 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature