ArticleEMBO reports2022
Parkin coordinates mitochondrial lipid remodeling to execute mitophagy.
Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2.Journal of cell science · 2025Article
- Diet-induced obesity dampens the temporal oscillation of hepatic mitochondrial lipids.Journal of lipid research · 2025Article
- Phosphatidate phosphatase Lipin1 alters mitochondria-associated endoplasmic reticulum membranes (MAMs) homeostasis: effects which contribute to the development of diabetic encephalopathy.Journal of neuroinflammation · 2025Article
- Acute diacylglycerol production activates critical membrane-shaping proteins leading to mitochondrial tubulation and fission.Nature communications · 2025Article
- Optogenetic Strategies for Optimizing the Performance of Phospholipids Biosensors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Salidroside enhances 5-fluorouracil sensitivity against hepatocellular carcinoma via YIPF5-induced mitophagy.Frontiers in pharmacology · 2024Article
- Involvement of Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2023Review
- Role of Mitochondria-ER Contact Sites in Mitophagy.Biomolecules · 2023Review
- Organelle-Selective Membrane Labeling through Phospholipase D-Mediated Transphosphatidylation.JACS Au · 2022Article
- Parkin coordinates mitochondrial lipid remodeling to execute mitophagy.EMBO reports · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
Autophagy has emerged as the prime machinery for implementing organelle quality control. In the context of mitophagy, the ubiquitin E3 ligase Parkin tags impaired mitochondria with ubiquitin to activate autophagic degradation. Although ubiquitination is essential for mitophagy, it is unclear how ubiquitinated mitochondria activate autophagosome assembly locally to ensure efficient destruction. Here, we report that Parkin activates lipid remodeling on mitochondria targeted for autophagic destruction. Mitochondrial Parkin induces the production of phosphatidic acid (PA) and its subsequent conversion to diacylglycerol (DAG) by recruiting phospholipase D2 and activating the PA phosphatase, Lipin-1. The production of DAG requires mitochondrial ubiquitination and ubiquitin-binding autophagy receptors, NDP52 and optineurin (OPTN). Autophagic receptors, via Golgi-derived vesicles, deliver an autophagic activator, EndoB1, to ubiquitinated mitochondria. Inhibition of Lipin-1, NDP52/OPTN, or EndoB1 results in a failure to produce mitochondrial DAG, autophagosomes, and mitochondrial clearance, while exogenous cell-permeable DAG can induce autophagosome production. Thus, mitochondrial DAG production acts downstream of Parkin to enable the local assembly of autophagosomes for the efficient disposal of ubiquitinated mitochondria.
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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.