Evidence map›Paper›PMID 22029897›Full record

ArticleMalaria journal2011

Mitochondrial NAD+-dependent malic enzyme from Anopheles stephensi: a possible novel target for malaria mosquito control.

Jennifer Pon, Eleonora Napoli, Shirley Luckhart, Cecilia Giulivi

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.3field-weighted citation impact, top 17% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
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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

4 authors at 1 institution in 1 country.

Jennifer PonDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, USA.
Eleonora Napoli
Shirley Luckhart
Cecilia Giulivi
University of California, Davis · US

Funding

Insulin, IGF and Insulin Signaling: effects on Anopheles lifespan and immunityR01AI073745 · NIAID · UNIVERSITY OF ARIZONA · PI RIEHLE, MICHAEL ALLEN · 2008 to 2012
$2.5M
NIAID NIH HHS AI073745
6 · The paper itself

Abstract

backgroundAnopheles stephensi mitochondrial malic enzyme (ME) emerged as having a relevant role in the provision of pyruvate for the Krebs' cycle because inhibition of this enzyme results in the complete abrogation of oxygen uptake by mitochondria. Therefore, the identification of ME in mitochondria from immortalized A. stephensi (ASE) cells and the investigation of the stereoselectivity of malate analogues are relevant in understanding the physiological role of ME in cells of this important malaria parasite vector and its potential as a possible novel target for insecticide development.

methodsTo characterize the mitochondrial ME from immortalized ASE cells (Mos. 43; ASE), mass spectrometry analyses of trypsin fragments of ME, genomic sequence analysis and biochemical assays were performed to identify the enzyme and evaluate its activity in terms of cofactor dependency and inhibitor preference.

resultsThe encoding gene sequence and primary sequences of several peptides from mitochondrial ME were found to be highly homologous to the mitochondrial ME from Anopheles gambiae (98%) and 59% homologous to the mitochondrial NADP+-dependent ME isoform from Homo sapiens. Measurements of ME activity in mosquito mitochondria isolated from ASE cells showed that (i) Vmax with NAD+ was 3-fold higher than that with NADP+, (ii) addition of Mg2+ or Mn2+ increased the Vmax by 9- to 21-fold, with Mn2+ 2.3-fold more effective than Mg2+, (iii) succinate and fumarate increased the activity by 2- and 5-fold, respectively, at sub-saturating concentrations of malate, (iv) among the analogs of L-malate tested as inhibitors of the NAD+-dependent ME catalyzed reaction, small (2- to 3-carbons) organic diacids carrying a 2-hydroxyl/keto group behaved as the most potent inhibitors of ME activity (e.g., oxaloacetate, tartronic acid and oxalate).

conclusionsThe biochemical characterization of Anopheles stephensi ME is of critical relevance given its important role in bioenergetics, suggesting that it is a suitable target for insecticide development.

Indexed as

Amino Acid SequenceAnimalsAnophelesCations, DivalentCell LineCoenzymesEnzyme InhibitorsFumaratesKineticsMagnesiumMalate DehydrogenaseMalatesManganeseMass SpectrometryMitochondriaModels, MolecularCations, DivalentCoenzymesEnzyme InhibitorsFumaratesMagnesiumMalate Dehydrogenasemalate dehydrogenase-(oxaloacetate-decarboxylating) (NAD+)Malatesmalic acidManganeseNADNADPSuccinic Acid

Identifiers

PMID22029897
PMCPMC3228860
OpenAlexW2159597537

What OpenQuestion holds

Textmetadata
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.