Evidence map›Paper›PMID 26063804›Full record

ArticleThe Journal of biological chemistry2015

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2).

Mahmoud M Elguindy, Eiko Nakamaru-Ogiso

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

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

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

  1. Pooled it
  2. Review
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  7. Review
  8. Inhibitors of Type II NADH Dehydrogenase Enzyme: A Review.Current protein & peptide science · 2025
    Review
  9. Article
  10. Article
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  12. [Role of Mitochondria in Ferroptosis and Its Relationship to Tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024
    Review
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13 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

2 authors at 1 institution in 1 country.

Mahmoud M ElguindyJohnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Eiko Nakamaru-OgisoJohnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104. Electronic address: eikoo@mail.med.upenn.edu.
University of Pennsylvania · US

Funding

Proton pumping mechanism in complex IR01GM097409 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI OGISO, EIKO · 2011 to 2015
$1.5M
NIGMS NIH HHS R01 GM097409NIGMS NIH HHS R01GM097409
6 · The paper itself

Abstract

Apoptosis-inducing factor (AIF) and AMID (AIF-homologous mitochondrion-associated inducer of death) are flavoproteins. Although AIF was originally discovered as a caspase-independent cell death effector, bioenergetic roles of AIF, particularly relating to complex I functions, have since emerged. However, the role of AIF in mitochondrial respiration and redox metabolism has remained unknown. Here, we investigated the redox properties of human AIF and AMID by comparing them with yeast Ndi1, a type 2 NADH:ubiquinone oxidoreductase (NDH-2) regarded as alternative complex I. Isolated AIF and AMID containing naturally incorporated FAD displayed no NADH oxidase activities. However, after reconstituting isolated AIF or AMID into bacterial or mitochondrial membranes, N-terminally tagged AIF and AMID displayed substantial NADH:O₂ activities and supported NADH-linked proton pumping activities in the host membranes almost as efficiently as Ndi1. NADH:ubiquinone-1 activities in the reconstituted membranes were highly sensitive to 2-n-heptyl-4-hydroxyquinoline-N-oxide (IC₅₀ = ∼1 μm), a quinone-binding inhibitor. Overexpressing N-terminally tagged AIF and AMID enhanced the growth of a double knock-out Escherichia coli strain lacking complex I and NDH-2. In contrast, C-terminally tagged AIF and NADH-binding site mutants of N-terminally tagged AIF and AMID failed to show both NADH:O₂ activity and the growth-enhancing effect. The disease mutant AIFΔR201 showed decreased NADH:O₂ activity and growth-enhancing effect. Furthermore, we surprisingly found that the redox activities of N-terminally tagged AIF and AMID were sensitive to rotenone, a well known complex I inhibitor. We propose that AIF and AMID are previously unidentified mammalian NDH-2 enzymes, whose bioenergetic function could be supplemental NADH oxidation in cells.

Indexed as

Apoptosis Inducing FactorApoptosis Regulatory ProteinsCloning, MolecularElectron Transport Complex IEscherichia coliEscherichia coli ProteinsGene ExpressionGene LibraryGenetic Complementation TestHumansIsoenzymesKineticsMembrane ProteinsMitochondrial MembranesMitochondrial ProteinsMutationAIFM1 protein, humanApoptosis Inducing FactorApoptosis Regulatory ProteinsElectron Transport Complex IEscherichia coli Proteinsferroptosis suppressor protein 1, humanIsoenzymesMembrane ProteinsMitochondrial ProteinsNADNuoH protein, E coliRecombinant Proteinsapoptosisapoptosis-inducing factorcomplex Imitochondrial metabolismmitochondrial respiratory chain complexnicotinamide adenine dinucleotide (NADH)rotenoneubiquinone

Identifiers

PMID26063804
PMCPMC4543644
OpenAlexW1590762938

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.