Evidence map›Paper›PMID 24578415›Full record

ArticleEMBO molecular medicine2014

Defects in GABA metabolism affect selective autophagy pathways and are alleviated by mTOR inhibition.

Ronak Lakhani, Kara R Vogel, Andreas Till, Jingjing Liu, Sarah F Burnett, K Michael Gibson, Suresh Subramani

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

47 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Guideline
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  10. Ablation ofbioRxiv : the preprint server for biology · 2023
    Article
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  13. Second Generation of Antiepileptic Drugs and Oxidative Stress.International journal of molecular sciences · 2023
    Review
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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

7 authors.

Ronak LakhaniDivision of Biological Sciences, Section of Molecular Biology, University of California San Diego, La Jolla, CA, USA.
Kara R Vogel
Andreas Till
Jingjing Liu
Sarah F Burnett
K Michael Gibson
Suresh Subramani

Funding

SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
Mechanisms Involved in PexophagyR01GM069373 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANI, SURESH · 2006 to 2013
$2.3M
Novel Treatment & Screening Strategies in Gamma-Hydroxybutyric AciduriaR01HD058553 · NICHD · WASHINGTON STATE UNIVERSITY · PI GIBSON, K MICHAEL · 2009 to 2013
$1.5M
NICHD NIH HHS HD 58553NICHD NIH HHS R01 HD058553NIGMS NIH HHS GM 069373NIGMS NIH HHS GM 085764NIGMS NIH HHS P50 GM085764NIGMS NIH HHS R01 GM069373
6 · The paper itself

Abstract

In addition to key roles in embryonic neurogenesis and myelinogenesis, γ-aminobutyric acid (GABA) serves as the primary inhibitory mammalian neurotransmitter. In yeast, we have identified a new role for GABA that augments activity of the pivotal kinase, Tor1. GABA inhibits the selective autophagy pathways, mitophagy and pexophagy, through Sch9, the homolog of the mammalian kinase, S6K1, leading to oxidative stress, all of which can be mitigated by the Tor1 inhibitor, rapamycin. To confirm these processes in mammals, we examined the succinic semialdehyde dehydrogenase (SSADH)-deficient mouse model that accumulates supraphysiological GABA in the central nervous system and other tissues. Mutant mice displayed increased mitochondrial numbers in the brain and liver, expected with a defect in mitophagy, and morphologically abnormal mitochondria. Administration of rapamycin to these mice reduced mTOR activity, reduced the elevated mitochondrial numbers, and normalized aberrant antioxidant levels. These results confirm a novel role for GABA in cell signaling and highlight potential pathomechanisms and treatments in various human pathologies, including SSADH deficiency, as well as other diseases characterized by elevated levels of GABA.

Indexed as

AutophagyAmino Acid Metabolism, Inborn ErrorsAnimalsBrainDevelopmental Disabilitiesgamma-Aminobutyric AcidHumansLiverMiceMice, KnockoutSuccinate-Semialdehyde DehydrogenaseTOR Serine-Threonine Kinasesgamma-Aminobutyric AcidSuccinate-Semialdehyde DehydrogenaseTOR Serine-Threonine Kinases

Identifiers

PMID24578415
PMCPMC3992080

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.