Evidence map›Paper›PMID 31329164›Full record

ArticleThe Journal of clinical investigation2019

ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes.

G Michelle Ducasa, Alla Mitrofanova, Shamroop K Mallela, Xiaochen Liu, Judith Molina, Alexis Sloan, Christopher E Pedigo, Mengyuan Ge, Javier Varona Santos, Yanio Hernandez and 15 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 1 pooled it
11.2field-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

113 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.

  1. Lipid homeostasis in diabetic kidney disease.International journal of biological sciences · 2024
    Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Lifestyles, metabolome and diabetic kidney disease: a cohort study.QJM : monthly journal of the Association of Physicians · 2026
    Article
  14. Review
  15. Hyperlipidemia in membranous nephropathy.Clinical kidney journal · 2026
    Review
  16. Podocyte Metabolic Reprogramming and Targeted Therapy.Journal of the American Society of Nephrology : JASN · 2026
    Review
  17. Review
  18. Review
  19. Spatial transcriptomics identifies IL-32 as a lipid droplet-associated cytokine linked to tubular injury in human diabetic kidney disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  20. Article

53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 6 institutions in 3 countries.

G Michelle DucasaKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Alla MitrofanovaKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Shamroop K MallelaKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Xiaochen LiuKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Judith MolinaKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Alexis SloanKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Christopher E PedigoDepartment of Internal Medicine, Yale University, New Haven, Connecticut, USA.
Mengyuan GeKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Javier Varona SantosKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Yanio HernandezKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Jin-Ju KimKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Cyrille MaugeaisRoche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Armando J MendezDiabetes Research Institute, University of Miami, Miami, Florida, USA.
Viji NairDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.
Matthias KretzlerDepartment of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.
George W BurkeDepartment of Surgery, University of Miami, Miami, Florida, USA.
Robert G NelsonNIDDK, Phoenix, Arizona, USA.
Yu IshimotoDivision of CKD Pathophysiology, University of Tokyo, Tokyo, Japan.
Reiko InagiDivision of CKD Pathophysiology, University of Tokyo, Tokyo, Japan.
Santanu BanerjeeDepartment of Surgery, University of Miami, Miami, Florida, USA.
Shaoyi LiuSocial Profit Network Research Lab, Alexandria LaunchLabs, New York, New York, USA.
Hazel H SzetoSocial Profit Network Research Lab, Alexandria LaunchLabs, New York, New York, USA.
Sandra MerscherKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
Flavia FontanesiDepartment of Biochemistry and Molecular Biology, University of Miami, Miami, Florida, USA.
Alessia FornoniKatz Family Division of Nephrology and Hypertension/ Drug Discovery Center, Department of Medicine, University of Miami, Miami, Florida, USA.
University of Miami · USLaunchpad Central (United States) · USThe University of Tokyo · JPUniversity of Michigan · USRoche (Switzerland) · CHYale University · US

Funding

Training Program in Clinical & Translationa Research in Human Glomerular DiseaseU54DK083912 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KRETZLER, MATTHIAS · 2009 to 2023
$20.3M
Miami Clinical and Translational Science InstituteUL1TR000460 · NCATS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SACCO, RALPH L. · 2012 to 2016
$16.9M
University of Michigan O'Brien Kidney Translational Core CenterP30DK081943 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PENNATHUR, SUBRAMANIAM · 2008 to 2022
$12.9M
Epidemiology, Pathophysiology and Treatment of Diabetic NephropathyZIADK069062 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI NELSON, ROBERT G · 2009 to 2023
$10.1M
Crosstalk Between Lipid Droplets and Other Organelles in PodocytesR01DK104753 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI FORNONI, ALESSIA · 2015 to 2025
$5.9M
Primary Outcomes in Glomerulonephritis Study (PROGRESS)UM1DK100846 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI HOLZMAN, LAWRENCE B. · 2013 to 2018
$5.8M
1/13 ApoL1 Genotypes in Kidney Donors and Long-Term Outcomes in Kidney Transplant Recipients Clinical CenterU01DK116101 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ALESSIA FORNONI, Mariella Cecilia Ortigosa-goggins · 2017 to 2026
$2.4M
(PQ12) Targeting SMPDL3b to Prevent Radiation-Induced NephrotoxicityR01CA227493 · NCI · UNIVERSITY OF ROCHESTER · PI MARPLES, BRIAN · 2018 to 2022
$2.0M
SMPDL3b and podocyte insulin signaling in DKDR01DK117599 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI FORNONI, ALESSIA · 2018 to 2021
$1.4M
NCATS NIH HHS UL1 TR000460NCI NIH HHS R01 CA227493NIDDK NIH HHS P30 DK081943NIDDK NIH HHS R01 DK104753NIDDK NIH HHS R01 DK117599NIDDK NIH HHS U01 DK116101NIDDK NIH HHS U54 DK083912NIDDK NIH HHS UM1 DK100846
6 · The paper itself

Abstract

Fibroblasts from patients with Tangier disease carrying ATP-binding cassette A1 (ABCA1) loss-of-function mutations are characterized by cardiolipin accumulation, a mitochondrial-specific phospholipid. Suppression of ABCA1 expression occurs in glomeruli from patients with diabetic kidney disease (DKD) and in human podocytes exposed to DKD sera collected prior to the development of DKD. We demonstrated that siRNA ABCA1 knockdown in podocytes led to reduced oxygen consumption capabilities associated with alterations in the oxidative phosphorylation (OXPHOS) complexes and with cardiolipin accumulation. Podocyte-specific deletion of Abca1 (Abca1fl/fl) rendered mice susceptible to DKD, and pharmacological induction of ABCA1 improved established DKD. This was not mediated by free cholesterol, as genetic deletion of sterol-o-acyltransferase-1 (SOAT1) in Abca1fl/fl mice was sufficient to cause free cholesterol accumulation but did not cause glomerular injury. Instead, cardiolipin mediates ABCA1-dependent susceptibility to podocyte injury, as inhibition of cardiolipin peroxidation with elamipretide improved DKD in vivo and prevented ABCA1-dependent podocyte injury in vitro and in vivo. Collectively, we describe a pathway definitively linking ABCA1 deficiency to cardiolipin-driven mitochondrial dysfunction. We demonstrated that this pathway is relevant to DKD and that ABCA1 inducers or inhibitors of cardiolipin peroxidation may each represent therapeutic strategies for the treatment of established DKD.

Indexed as

Lipid PeroxidationAnimalsATP Binding Cassette Transporter 1CardiolipinsDiabetic NephropathiesHumansMiceMitochondriaPodocytesSterol O-AcyltransferaseABCA1 protein, humanAbca1 protein, mouseATP Binding Cassette Transporter 1CardiolipinsSterol O-Acyltransferasesterol O-acyltransferase 1CholesterolChronic kidney diseaseMetabolismMitochondriaNephrology

Identifiers

PMID31329164
PMCPMC6668702
OpenAlexW2963804962

What Socratic holds

Textmetadata
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 Socratic graph.