Cell reportsSep 1, 2026

MGRN1 helps protect temporarily damaged energy centers in cells for antioxidant repair

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 2, 2026

Abstract

The E3 ubiquitin ligase MGRN1 acts as a damage-threshold sensor for mitochondrial stress.

MGRN1 distinguishes between transient and prolonged mitochondrial damage.
During transient stress, MGRN1 associates with the outer mitochondrial membrane to inhibit mitophagy.
Loss of MGRN1 leads to excessive mitophagy and poor recovery from mitochondrial stress.
Mitochondrial repair involves the coordination of multiple signaling pathways, including DELE1-eIF2α-ATF4, Nrf2, and JUN/FOS.
TXNRD1 and SLC7A11 are identified as key effectors in the antioxidant response following mitochondrial damage.

Simplified

Mitochondria are continuously exposed to damage that contributes to aging and disease. While prolongedly damaged mitochondria are eliminated by mitophagy, how cells respond to transient damage remains unclear. Here, we establish a cell-based system to induce transient mitochondrial stress and resolve its recovery dynamics. We identify the E3 ubiquitin ligase mahogunin ring finger 1 (MGRN1) as a damage-threshold sensor that discriminates between transient and prolonged mitochondrial insults. Under transient stress, MGRN1 shows enhanced association with the outer mitochondrial membrane via MFN1, where it restrains mitophagy, potentially preserving mitochondria for repair. Loss of MGRN1 disrupts this checkpoint, leading to inappropriate mitophagy and impaired recovery. Mechanistically, mitochondrial repair is coordinated by the DELE1-eIF2α-ATF4 axis, Nrf2 signaling, and JUN/FOS activation, which collectively drive an antioxidant program, with TXNRD1 and SLC7A11 as downstream effectors. Together, our findings uncover a damage-sensing checkpoint that gates the decision between recovery and clearance, and reveal active and regulated pathways for mitochondrial repair.

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MGRN1 helps protect temporarily damaged energy centers in cells for antioxidant repair

Abstract

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