Evidence map›Paper›PMID 33404293›Full record

ArticleAutophagy2021

BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes.

Meysam Yazdankhah, Sayan Ghosh, Peng Shang, Nadezda Stepicheva, Stacey Hose, Haitao Liu, Xitiz Chamling, Shenghe Tian, Mara L G Sullivan, Michael Joseph Calderon and 9 more

Open access · greenAbstract read
In one paragraph

Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

59 citing papers in PubMed, 78 citations in OpenAlex.

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  14. Dying oligodendrocytes persist without mitochondria.bioRxiv : the preprint server for biology · 2026
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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

19 authors at 4 institutions in 2 countries.

Meysam YazdankhahDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sayan GhoshDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Peng ShangDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Nadezda StepichevaDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Stacey HoseDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Haitao LiuDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-3757-779X
Xitiz ChamlingDepartment of Ophthalmology, Wilmer Eye Institute, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-6401-7715
Shenghe TianDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mara L G SullivanDepartment of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Michael Joseph CalderonDepartment of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Christopher S FittingDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Joseph WeissDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ashwath JayagopalKodiak Sciences, Palo Alto, CA, USA.
James T HandaDepartment of Ophthalmology, Wilmer Eye Institute, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
José-Alain SahelDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-4831-1153
J Samuel ZiglerDepartment of Ophthalmology, Wilmer Eye Institute, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Paul R KinchingtonDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Donald J ZackDepartment of Ophthalmology, Wilmer Eye Institute, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Debasish SinhaDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
University of Pittsburgh · USJohns Hopkins University · USCentre National de la Recherche Scientifique · FRKodiak Sciences · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
Interdisciplinary Visual Sciences (IVS) Traininig ProgramT32EY017271 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Marlene Behrmann, Paul R. Kinchington · 2008 to 2026
$3.6M
Genetic analysis of a spontaneous mutation in a rat with a novel hind limb defectR21HD059008 · NICHD · JOHNS HOPKINS UNIVERSITY · PI SINHA, DEBASISH · 2009 to 2010
$449k
Developing Remyelination Strategies for Demyelinating Optic Neuropathies Using Human Pluripotent Stem CellsK99EY029011 · NEI · JOHNS HOPKINS UNIVERSITY · PI CHAMLING, XITIZ · 2019 to 2021
$294k
NEI NIH HHS K99 EY029011NEI NIH HHS P30 EY001765NEI NIH HHS P30 EY008098NEI NIH HHS T32 EY017271NICHD NIH HHS R21 HD059008
6 · The paper itself

Abstract

Retinal ganglion cell axons are heavily myelinated (98%) and myelin damage in the optic nerve (ON) severely affects vision. Understanding the molecular mechanism of oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes will be essential for developing new therapeutic approaches for ON demyelinating diseases. To this end, we developed a new method for isolation and culture of ON-derived oligodendrocyte lineage cells and used it to study OPC differentiation. A critical aspect of cellular differentiation is macroautophagy/autophagy, a catabolic process that allows for cell remodeling by degradation of excess or damaged cellular molecules and organelles. Knockdown of ATG9A and BECN1 (pro-autophagic proteins involved in the early stages of autophagosome formation) led to a significant reduction in proliferation and survival of OPCs. We also found that autophagy flux (a measure of autophagic degradation activity) is significantly increased during progression of oligodendrocyte differentiation. Additionally, we demonstrate a significant change in mitochondrial dynamics during oligodendrocyte differentiation, which is associated with a significant increase in programmed mitophagy (selective autophagic clearance of mitochondria). This process is mediated by the mitophagy receptor BNIP3L (BCL2/adenovirus E1B interacting protein 3-like). BNIP3L-mediated mitophagy plays a crucial role in the regulation of mitochondrial network formation, mitochondrial function and the viability of newly differentiated oligodendrocytes. Our studies provide novel evidence that proper mitochondrial dynamics is required for establishment of functional mitochondria in mature oligodendrocytes. These findings are significant because targeting BNIP3L-mediated programmed mitophagy may provide a novel therapeutic approach for stimulating myelin repair in ON demyelinating diseases.

Indexed as

AutophagyMitophagyCell DifferentiationMitochondriaOligodendrogliaOptic NerveATG9Aautophagyautophagy fluxco-culturedemyelinating diseasesglial cellsmitochondrial dynamicsmyelinoligodendrocyte lineage cellsretinal ganglion cell axons

Identifiers

PMID33404293
PMCPMC8526037
OpenAlexW3118237202

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.