Evidence map›Paper›PMID 41059761›Full record

ArticleAutophagy2025

PPP2/PP2A-mediated dephosphorylation of LC3B links PINK1-PRKN/Parkin-mediated mitophagy to SCA12 pathogenesis.

Ningning Li, Hongyu Hou, Dan Su, Bojun Yang, Rui Ni, Guoqiang Ma, Shan Sun, Qilian Ma, Qiang Peng, Siqian Chen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Salidroside Protects Against Simazine-Induced Neurotoxicity by ActivatingInternational journal of molecular sciences · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Ningning LiJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Hongyu HouJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Dan SuJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Bojun YangJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Rui NiJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Guoqiang MaJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Shan SunJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Qilian MaJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Qiang PengJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Siqian ChenJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Kin Yip TamFaculty of Health Sciences, University of Macau, Macau, China.
Hongfeng WangJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Zheng YingJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.ORCID 0000-0002-1099-0509

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Atg8-family proteins are autophagosome-associated proteins and play important roles in macroautophagy/autophagy, a conserved process for degrading defective or excessive cellular components. Post-translational modifications of mammalian Atg8-family proteins, including phosphorylation, regulate multiple steps in the autophagic process. In this context, several Atg8-family protein-associated kinases have been found to regulate autophagy, yet the phosphatases in the dephosphorylation of Atg8-family proteins remain unknown. Here, we report that the heterotrimeric PPP2/PP2A (protein phosphatase 2) is a novel regulator in modulating LC3B dephosphorylation. Mechanistically, we find that PPP2-mediated LC3B dephosphorylation reduces the interaction between LC3B and the mitophagy receptor OPTN, thereby impeding the mitochondrial recruitment of phagophores during PINK1-PRKN/Parkin-mediated mitophagy. Interestingly, we find that overexpression of the β2 isoform of PPP2R2B (protein phosphatase 2 regulatory subunit Bbeta; PPP2R2Bβ2), which mimics the spinocerebellar ataxia type 12 (SCA12) pathological condition, harms neuronal survival by enhancing PPP2-mediated LC3B dephosphorylation and reducing mitochondrial recruitment of phagophores upon mitochondrial damage. Importantly, pharmacological induction of mitophagy by the small molecule compound deferiprone (DFP) relieves PPP2R2Bβ2-mediated neuronal toxicity. Overall, our results not only uncover a mechanism by which protein dephosphorylation negatively regulates mitophagy but also provide insights into the pathogenesis of PPP2R2Bβ2-mediated SCA12.

Indexed as

Microtubule-Associated ProteinsMitophagyProtein KinasesProtein Phosphatase 2Spinocerebellar AtaxiasUbiquitin-Protein LigasesAnimalsAutophagyCell Cycle ProteinsHEK293 CellsHumansMembrane Transport ProteinsMiceMitochondriaNerve Tissue ProteinsPhosphorylationCell Cycle ProteinsMAP1LC3B protein, humanMembrane Transport ProteinsMicrotubule-Associated ProteinsNerve Tissue ProteinsOPTN protein, humanparkin proteinPPP2R2B protein, humanProtein KinasesProtein Phosphatase 2PTEN-Induced Putative KinaseUbiquitin-Protein LigasesDephosphorylationLC3Bmitochondrial quality controlPINK1-PRKN/Parkin-mediated mitophagyPPP2/PP2APPP2R2Bβ2

Identifiers

PMID41059761
PMCPMC12758320

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.