Evidence map›Paper›PMID 32080200›Full record

ArticleNature communications2020

Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency.

Alessandro Luciani, Anke Schumann, Marine Berquez, Zhiyong Chen, Daniela Nieri, Mario Failli, Huguette Debaix, Beatrice Paola Festa, Natsuko Tokonami, Andrea Raimondi and 10 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% of its field
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

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.

  1. Guideline
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  5. Immune Dysregulation in Branched Chain Organic Acidemias.Journal of inherited metabolic disease · 2026
    Review
  6. The kidney in genetic metabolic disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 9 institutions in 6 countries.

Alessandro Luciani *Institute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland. alessandro.luciani@uzh.ch.
Anke Schumann *Institute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland.
Marine Berquez *Institute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland.
Zhiyong Chen *Institute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-0203-2930
Daniela NieriInstitute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland.
Mario FailliDepartment of Biomedicine, University of Eastern Finland, 70211, Kuopio, Finland.
Huguette DebaixInstitute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland.
Beatrice Paola FestaInstitute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland.
Natsuko TokonamiInstitute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland.
Andrea RaimondiSan Raffaele Scientific Institute, Experimental Imaging Center, 20132, Milan, Italy.ORCID http://orcid.org/0000-0002-4563-386X
Alessio CremonesiDivision of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, 8032, Zurich, Switzerland.
Diego CarrellaTelethon Institute of Genetics and Medicine, Pozzuoli, 80078, Naples, Italy.
Patrick FornyDivision of Metabolism and Children's Research Center, University Children's Hospital, 8032, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-1877-2976
Stefan KölkerDivision of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, 69120, Heidelberg, Germany.
Francesca Diomedi CamasseiDepartment of Laboratories-Pathology Unit, Bambino Gesù Children's Hospital, 00165, Rome, Italy.
Francisca DiazDepartment of Neurology, University of Miami Miller School of Medicine, 33136, Miami, FL, USA.
Carlos T MoraesDepartment of Neurology, University of Miami Miller School of Medicine, 33136, Miami, FL, USA.
Diego Di BernardoTelethon Institute of Genetics and Medicine, Pozzuoli, 80078, Naples, Italy.ORCID http://orcid.org/0000-0002-1911-7407
Matthias R BaumgartnerDivision of Metabolism and Children's Research Center, University Children's Hospital, 8032, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-9270-0826
Olivier DevuystInstitute of Physiology and NCCR Kidney.CH, University of Zurich, 8057, Zurich, Switzerland. olivier.devuyst@uzh.ch.ORCID http://orcid.org/0000-0003-3744-4767
University of Zurich · CHUniversity Children's Hospital Zurich · CHTelethon Institute Of Genetics And Medicine · ITUniversity of Miami · USBambino Gesù Children's Hospital · ITCliniques Universitaires Saint-Luc · BEHeidelberg University · DESan Raffaele University of Rome · ITUniversity of Eastern Finland · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deregulation of mitochondrial network in terminally differentiated cells contributes to a broad spectrum of disorders. Methylmalonic acidemia (MMA) is one of the most common inherited metabolic disorders, due to deficiency of the mitochondrial methylmalonyl-coenzyme A mutase (MMUT). How MMUT deficiency triggers cell damage remains unknown, preventing the development of disease-modifying therapies. Here we combine genetic and pharmacological approaches to demonstrate that MMUT deficiency induces metabolic and mitochondrial alterations that are exacerbated by anomalies in PINK1/Parkin-mediated mitophagy, causing the accumulation of dysfunctional mitochondria that trigger epithelial stress and ultimately cell damage. Using drug-disease network perturbation modelling, we predict targetable pathways, whose modulation repairs mitochondrial dysfunctions in patient-derived cells and alleviate phenotype changes in mmut-deficient zebrafish. These results suggest a link between primary MMUT deficiency, diseased mitochondria, mitophagy dysfunction and epithelial stress, and provide potential therapeutic perspectives for MMA.

Indexed as

Alkyl and Aryl TransferasesAmino Acid Metabolism, Inborn ErrorsAnimalsDisease Models, AnimalEpithelial CellsFemaleGene Knockout TechniquesHumansMaleMembrane ProteinsMetabolism, Inborn ErrorsMethylmalonyl-CoA MutaseMiceMice, KnockoutMitochondrial DiseasesMitophagyAlkyl and Aryl TransferasesCOX10 protein, mouseMembrane ProteinsMethylmalonyl-CoA Mutaseparkin proteinProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein Ligases

Identifiers

PMID32080200
PMCPMC7033137
OpenAlexW3008564638

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.