A TRNA Processing Enzyme is a Key Regulator of the Mitochondrial Unfolded Protein Response

Overview

Journal Elife

Specialty Biology

Date 2022 Apr 22

PMID 35451962

Authors

James P Held

Gaomin Feng

Benjamin R Saunders

Claudia V Pereira

Kristopher Burkewitz

Maulik R Patel

Affiliations

Soon will be listed here.

Abstract

The mitochondrial unfolded protein response (UPR) has emerged as a predominant mechanism that preserves mitochondrial function. Consequently, multiple pathways likely exist to modulate UPR. We discovered that the tRNA processing enzyme, homolog of ELAC2 (HOE-1), is key to UPR regulation in . We find that nuclear HOE-1 is necessary and sufficient to robustly activate UPR. We show that HOE-1 acts via transcription factors ATFS-1 and DVE-1 that are crucial for UPR. Mechanistically, we show that HOE-1 likely mediates its effects via tRNAs, as blocking tRNA export prevents HOE-1-induced UPR. 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 UPR.

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