Evidence map›Paper›PMID 30870143›Full record

ArticleJCI insight2019

TFEB-driven lysosomal biogenesis is pivotal for PGC1α-dependent renal stress resistance.

Matthew R Lynch, Mei T Tran, Kenneth M Ralto, Zsuzsanna K Zsengeller, Vinod Raman, Swati S Bhasin, Nuo Sun, Xiuying Chen, Daniel Brown, Ilsa I Rovira and 6 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. 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 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Selective autophagy in kidney health and disease.Nature reviews. Nephrology · 2026
    Review
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  13. MondoA and AKI and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2024
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 1 country.

Matthew R LynchDivision of Nephrology.
Mei T TranDivision of Nephrology.
Kenneth M RaltoDivision of Nephrology.
Zsuzsanna K ZsengellerDivision of Nephrology.
Vinod RamanDivision of Nephrology.
Swati S BhasinDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Nuo SunCenter for Molecular Medicine, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Xiuying ChenDivision of Nephrology.
Daniel BrownDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Ilsa I RoviraCenter for Molecular Medicine, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Kensei TaguchiDivision of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Craig R BrooksDivision of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Isaac E StillmanDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Manoj K BhasinDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Toren FinkelCenter for Molecular Medicine, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
Samir M ParikhDivision of Nephrology.
Beth Israel Deaconess Medical Center · USNational Heart Lung and Blood Institute · USVanderbilt University Medical Center · USUniversity of Pittsburgh · US

Funding

The Aging Kidney: Chronic Injury, Impaired Functions and Clinical OutcomesR01AG027002 · NIA · TUFTS MEDICAL CENTER · PI PARIKH, SAMIR M, SARNAK, MARK J · 2005 to 2022
$7.3M
Tie2-driven vascular control in critical illnessR35HL139424 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI PARIKH, SAMIR M · 2018 to 2024
$6.4M
Vanderbilt O'Brien Kidney Center - Core D - Clinical and Translational CoreP30DK114809 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FOGO, AGNES B. · 2017 to 2021
$5.9M
Mitochondrial Biogenesis in Kidney DiseaseR01DK095072 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Samir M Parikh · 2012 to 2026
$5.3M
Proximal tubule Kim-1 expression modulates acute and chronic kidney injuryK01DK099473 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROOKS, CRAIG ROBERT · 2013 to 2017
$787k
NHLBI NIH HHS R35 HL139424NIA NIH HHS R01 AG027002NIDDK NIH HHS K01 DK099473NIDDK NIH HHS P30 DK114809NIDDK NIH HHS R01 DK095072
6 · The paper itself

Abstract

Because injured mitochondria can accelerate cell death through the elaboration of oxidative free radicals and other mediators, it is striking that proliferator gamma coactivator 1-alpha (PGC1α), a stimulator of increased mitochondrial abundance, protects stressed renal cells instead of potentiating injury. Here we report that PGC1α's induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. CRISPR and stable gene transfer showed that PGC1α knockout tubular cells were sensitized to the genotoxic stressor cisplatin whereas transgenic cells were protected. The biosensor mtKeima unexpectedly revealed that cisplatin blunts mitophagy both in cells and mice. PGC1α not only counteracted this effect but also raised basal mitophagy, as did the downstream mediator nicotinamide adenine dinucleotide (NAD+). PGC1α did not consistently affect known autophagy pathways modulated by cisplatin. Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1α in cells and conditional mice. These results uncover an unexpected effect of cisplatin on mitophagy and PGC1α's exquisite reliance on lysosomes for kidney protection. Finally, the data illuminate TFEB as a novel target for renal tubular stress resistance.

Indexed as

Organelle BiogenesisAcute Kidney InjuryAnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCisplatinCRISPR-Cas SystemsGene Transfer TechniquesKidney TubulesLysosomesMiceMice, KnockoutMice, TransgenicMitochondriaMitophagyNADBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCisplatinNADPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseTcfeb protein, mouseMitochondriaNephrology

Identifiers

PMID30870143
PMCPMC6538327
OpenAlexW4254195916

What OpenQuestion holds

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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.