Evidence map›Paper›PMID 20591975›Full record

ArticleEndocrinology2010

RhoA and DIAPH1 mediate adrenocorticotropin-stimulated cortisol biosynthesis by regulating mitochondrial trafficking.

Donghui Li, Marion B Sewer

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

23 citing papers in PubMed, 44 citations in OpenAlex.

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  12. SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP.Proceedings of the National Academy of Sciences of the United States of America · 2016
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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

2 authors at 1 institution in 1 country.

Donghui LiSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093-0704, USA.
Marion B Sewer
University of California, San Diego · US

Funding

Regulation of Steroidogenic Genes by Trophic HormonesR01GM073241 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEWER, MARION B. · 2004 to 2013
$2.2M
Regulation of Steroidogenic Genes by Trophic HormonesR56GM073241 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEWER, MARION B. · 2009 to 2009
$281k
NIGMS NIH HHS GM073241NIGMS NIH HHS R01 GM073241NIGMS NIH HHS R56 GM073241
6 · The paper itself

Abstract

Steroid hormones are formed by the successive action of enzymes that are localized in mitochondria and the endoplasmic reticulum (ER). Compartmentalization of these enzymes in different subcellular organelles dictates the need for efficient transfer of intermediary metabolites between the mitochondrion and ER; however, the molecular determinants that regulate interorganelle substrate exchange are unknown. The objective of this study was to define the molecular mechanism by which adrenocorticotropin (ACTH) signaling regulates communication between mitochondria and the ER during steroidogenesis. Using live cell video confocal microscopy, we found that ACTH and dibutyryl cAMP rapidly increased the rate of mitochondrial movement. Inhibiting tubulin polymerization prevented both basal and ACTH/cAMP-stimulated mitochondrial trafficking and decreased cortisol secretion. This decrease in cortisol secretion evoked by microtubule inhibition was paralleled by an increase in dehydroepiandrosterone production. In contrast, treatment with paclitaxel to stabilize microtubules or latrunculin B to inhibit actin polymerization and disrupt microfilament organization increased both mitochondrial trafficking and cortisol biosynthesis. ACTH-stimulated mitochondrial movement was dependent on RhoA and the RhoA effector, diaphanous-related homolog 1 (DIAPH1). ACTH signaling temporally increased the cellular concentrations of GTP-bound and Ser-188 phosphorylated RhoA, which promoted interaction with DIAPH1. Expression of a dominant-negative RhoA mutant or silencing DIAPH1 impaired mitochondrial trafficking and cortisol biosynthesis and concomitantly increased the secretion of adrenal androgens. We conclude that ACTH regulates cortisol production by facilitating interorganelle substrate transfer via a process that is mediated by RhoA and DIAPH1, which act to coordinate the dynamic trafficking of mitochondria.

Indexed as

Adaptor Proteins, Signal TransducingAdrenocorticotropic HormoneBiological TransportBucladesineCell Line, TumorColchicineEndoplasmic ReticulumForminsHumansHydrocortisoneMicroscopy, FluorescenceMicroscopy, VideoMicrotubulesMitochondriaMutationProtein BindingAdaptor Proteins, Signal TransducingAdrenocorticotropic HormoneBucladesineColchicineDIAPH1 protein, humanForminsHydrocortisonerhoA GTP-Binding ProteinTubulin Modulators

Identifiers

PMID20591975
PMCPMC2940507
OpenAlexW2042581720

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.