Evidence map›Paper›PMID 30741592›Full record

ArticleAutophagy2019

BNIP3L/NIX and FUNDC1-mediated mitophagy is required for mitochondrial network remodeling during cardiac progenitor cell differentiation.

Mark A Lampert, Amabel M Orogo, Rita H Najor, Babette C Hammerling, Leonardo J Leon, Bingyan J Wang, Taeyong Kim, Mark A Sussman, Åsa B Gustafsson

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

Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers.

0numbers the graph read from it
0cells of the map it votes in
194citing papers in PubMed
24.1field-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

194 citing papers in PubMed, 308 citations in OpenAlex.

  1. Review
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  4. Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026
    Review
  5. Multi-omics uncovers the critical role of ceramide-mediatedJournal of pharmaceutical analysis · 2026
    Article
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134 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Mark A Lamperta Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , CA , USA.
Amabel M Orogoa Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , CA , USA.
Rita H Najora Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , CA , USA.
Babette C Hammerlinga Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , CA , USA.
Leonardo J Leona Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , CA , USA.
Bingyan J Wangb San Diego Heart Research Institute and the Department of Biology , San Diego State University , San Diego , CA , USA.ORCID 0000-0002-3522-2848
Taeyong Kimb San Diego Heart Research Institute and the Department of Biology , San Diego State University , San Diego , CA , USA.ORCID 0000-0002-4147-3635
Mark A Sussmanb San Diego Heart Research Institute and the Department of Biology , San Diego State University , San Diego , CA , USA.ORCID 0000-0002-0104-4799
Åsa B Gustafssona Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , CA , USA.
University of California San Diego · USSan Diego State University · US

Funding

Surgery, Physiology and ImmunohistopathologyP01HL085577 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2006 to 2017
$18.4M
GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
Role of Bnip3 in Myocardial Ischemia/ReperfusionR01HL087023 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUSTAFSSON, ASA B. · 2007 to 2016
$3.8M
MCL-1 is a critical regulator of mitochondrial dynamics and function in myocytesR01HL132300 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUSTAFSSON, ASA B. · 2017 to 2020
$1.7M
Mitochondrial Quality Control in the Aging MyocardiumR21AG052280 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUSTAFSSON, ASA B. · 2016 to 2017
$426k
Mitochondrial Quality Control is Essential for Cardiac Progenitor Cell FunctionF31HL123309 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OROGO, AMABEL · 2014 to 2016
$98k
NHLBI NIH HHS F31 HL123309NHLBI NIH HHS P01 HL085577NHLBI NIH HHS R01 HL087023NHLBI NIH HHS R01 HL132300NIA NIH HHS R21 AG052280NIGMS NIH HHS T32 GM007752
6 · The paper itself

Abstract

Cell-based therapies represent a very promising strategy to repair and regenerate the injured heart to prevent progression to heart failure. To date, these therapies have had limited success due to a lack of survival and retention of the infused cells. Therefore, it is important to increase our understanding of the biology of these cells and utilize this information to enhance their survival and function in the injured heart. Mitochondria are critical for progenitor cell function and survival. Here, we demonstrate the importance of mitochondrial autophagy, or mitophagy, in the differentiation process in adult cardiac progenitor cells (CPCs). We found that mitophagy was rapidly induced upon initiation of differentiation in CPCs. We also found that mitophagy was mediated by mitophagy receptors, rather than the PINK1-PRKN/PARKIN pathway. Mitophagy mediated by BNIP3L/NIX and FUNDC1 was not involved in regulating progenitor cell fate determination, mitochondrial biogenesis, or reprogramming. Instead, mitophagy facilitated the CPCs to undergo proper mitochondrial network reorganization during differentiation. Abrogating BNIP3L- and FUNDC1-mediated mitophagy during differentiation led to sustained mitochondrial fission and formation of donut-shaped impaired mitochondria. It also resulted in increased susceptibility to cell death and failure to survive the infarcted heart. Finally, aging is associated with accumulation of mitochondrial DNA (mtDNA) damage in cells and we found that acquiring mtDNA mutations selectively disrupted the differentiation-activated mitophagy program in CPCs. These findings demonstrate the importance of BNIP3L- and FUNDC1-mediated mitophagy as a critical regulator of mitochondrial network formation during differentiation, as well as the consequences of accumulating mtDNA mutations.

Indexed as

Cell DifferentiationMitophagyAnimalsAutophagosomesCells, CulturedDNA Polymerase gammaHumansMaleMembrane ProteinsMiceMitochondriaMitochondrial DynamicsMitochondrial ProteinsMyoblasts, CardiacMyocardial InfarctionOrganelle BiogenesisDNA Polymerase gammaFUNDC1 protein, mouseMembrane ProteinsMitochondrial ProteinsNix protein, mousePHB2 protein, humanPhb2 protein, mouseProhibitinsAutophagydifferentiationheart failuremitochondriamitophagystem cells

Identifiers

PMID30741592
PMCPMC6613840
OpenAlexW2911385488

What OpenQuestion 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 OpenQuestion graph.