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Publication Detail

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

Authors: Held, James P; Feng, Gaomin; Saunders, Benjamin R; Pereira, Claudia V; Burkewitz, Kristopher; Patel, Maulik R

Published In Elife, (2022 Apr 22)

Abstract: The mitochondrial unfolded protein response (UPRmt) has emerged as a predominant mechanism that preserves mitochondrial function. Consequently, multiple pathways likely exist to modulate UPRmt. We discovered that the tRNA processing enzyme, homolog of ELAC2 (HOE-1), is key to UPRmt regulation in Caenorhabditis elegans. We find that nuclear HOE-1 is necessary and sufficient to robustly activate UPRmt. We show that HOE-1 acts via transcription factors ATFS-1 and DVE-1 that are crucial for UPRmt. Mechanistically, we show that HOE-1 likely mediates its effects via tRNAs, as blocking tRNA export prevents HOE-1-induced UPRmt. Interestingly, we find that HOE-1 does not act via the integrated stress response, which can be activated by uncharged tRNAs, pointing toward its reliance on a new mechanism. Finally, we show that the subcellular localization of HOE-1 is responsive to mitochondrial stress and is subject to negative regulation via ATFS-1. Together, we have discovered a novel RNA-based cellular pathway that modulates UPRmt.

PubMed ID: 35451962 Exiting the NIEHS site

MeSH Terms: Animals; Caenorhabditis elegans Proteins*/genetics; Caenorhabditis elegans Proteins*/metabolism; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Mitochondria/metabolism; Transcription Factors/metabolism; Unfolded Protein Response

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