Evidence map›Paper›PMID 33980811›Full record

ArticleCell death & disease2021

Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons.

Anthony R Anzell, Garrett M Fogo, Zoya Gurm, Sarita Raghunayakula, Joseph M Wider, Kathleen J Maheras, Katlynn J Emaus, Timothy D Bryson, Madison Wang, Robert W Neumar and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.4field-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

29 citing papers in PubMed, 45 citations in OpenAlex.

  1. Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026
    Review
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  4. Cross-species evidence for cardiolipin remodeling in neonatal hypoxic-ischemic encephalopathy.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Article
  5. Raptor and Drp1 Function Synthetically to Control Hypoxic Death and the Mitochondrial Network in Caenorhabditis elegans.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  20. Mitochondrial membrane potential and oxidative stress interact to regulate Oma1-dependent processing of Opa1 and mitochondrial dynamics.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
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

12 authors at 3 institutions in 1 country.

Anthony R AnzellDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Garrett M FogoDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Zoya GurmDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Sarita RaghunayakulaDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Joseph M WiderDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Kathleen J MaherasDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Katlynn J EmausDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Timothy D BrysonDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Madison WangDepartment of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Robert W NeumarDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Karin PrzyklenkDepartment of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Thomas H SandersonDepartment of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. thsand@umich.edu.ORCID http://orcid.org/0000-0003-0112-8164
University of Michigan · USWayne State University · USUniversity of Pittsburgh · US

Funding

TRAINING IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007853 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David J. Pinsky · 1996 to 2026
$11.6M
Non-invasive mitochondrial modulation therapy for ischemic strokeR01NS120322 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUETTEMANN, MAIK, SANDERSON, THOMAS HUDSON · 2021 to 2025
$2.3M
Infant NeuroLUX: A Novel Non-invasive Therapeutic Device for Neonatal Hypoxic Brain InjuryR42NS105238 · NINDS · MITOVATION, INC. · PI HUETTEMANN, MAIK, SANDERSON, THOMAS HUDSON · 2018 to 2020
$1.8M
Mitochondrial Integrity Regulates Cerebral Reperfusion InjuryR01NS076715 · NINDS · WAYNE STATE UNIVERSITY · PI KUMAR, RITA, SANDERSON, THOMAS HUDSON · 2013 to 2017
$1.7M
Limiting brain reperfusion injury by controlling mitochondrial functionR01NS091242 · NINDS · WAYNE STATE UNIVERSITY · PI HUETTEMANN, MAIK, SANDERSON, THOMAS HUDSON · 2015 to 2018
$1.3M
Investigating mitochondrial dynamics in cerebral ischemia/reperfusion injury using novel morphological analyses and computational modelingF31NS124280 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOGO, GARRETT MCGUIRE · 2021 to 2021
$38k
NHLBI NIH HHS T32 HL007853NINDS NIH HHS F31 NS124280NINDS NIH HHS R01 NS076715NINDS NIH HHS R01 NS091242NINDS NIH HHS R01 NS120322NINDS NIH HHS R42 NS105238
6 · The paper itself

Abstract

Mitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.

Indexed as

AnimalsDynaminsHumansMiceMitochondrial DynamicsMitophagyNeuronsReperfusion InjuryDNM1L protein, humanDynamins

Identifiers

PMID33980811
PMCPMC8115279
OpenAlexW3162373160

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.