ArticleAutophagy2026
Regulation of pexophagy by a novel TBK1-MARCHF7-PXMP4-NBR1 axis in PEX1-depleted HeLa cells.
Article in Autophagy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Inhibition of USP2 suppresses pathological pexophagy and rescues PEX1-deficient peroxisome biogenesis disorder.Signal transduction and targeted therapy · 2026Article
- Integrated transcriptomic and metabolomic profiling reveals coordinated regulatory networks associated with mosaic disease resistance in sugarcane.Frontiers in plant science · 2026Article
- From homeostasis to pathology, organelle-specific autophagy in skeletal muscle: a PRISMA-ScR scoping review.Frontiers in physiology · 2026Review
- Parallel Selection for Longevity in Mammals and Birds.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisomes are essential for lipid metabolism and redox balance, with pexophagy playing a critical role in maintaining cellular homeostasis. However, the regulatory mechanisms of pexophagy remain unclear. Through functional screening, we identified MARCHF7 as a novel E3 ligase regulating pexophagy. MARCHF7 depletion impaired pexophagic flux under PEX1 knockdown conditions. MARCHF7 binds to PXMP4 and promotes its ubiquitination at lysine 20 in PEX1-deficient cells. Depletion of PXMP4 impairs pexophagy, and reconstitution with the PXMP4 lysine 20 ubiquitination-defective mutant failed to rescue pexophagy. PEX1 depletion also induces TBK1 phosphorylation at serine 172, activating TBK1, which subsequently phosphorylates MARCHF7. This activation is driven by ROS accumulation, which reduces PXMP4 ubiquitination and prevents peroxisome loss. Furthermore, downregulation of MARCHF7 or PXMP4 impairs NBR1 recruitment to peroxisomes, suggesting that ubiquitinated PXMP4 acts as a recognition signal for NBR1. Collectively, our findings establish the TBK1-MARCHF7-PXMP4-NBR1 axis as a key regulatory pathway for pexophagy in response to PEX1 depletion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.