Evidence map›Paper›PMID 29611340›Full record

ArticlePhysiological reports2018

The targeted anti-oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue.

Esther M Gottwald, Michael Duss, Milica Bugarski, Dominik Haenni, Claus D Schuh, Ehud M Landau, Andrew M Hall

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

Article in Physiological reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.1field-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

48 citing papers in PubMed, 90 citations in OpenAlex.

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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 at 3 institutions in 1 country.

Esther M GottwaldInstitute of Anatomy, University of Zurich, Zurich, Switzerland.
Michael DussDepartment of Chemistry, University of Zurich, Zurich, Switzerland.
Milica BugarskiInstitute of Anatomy, University of Zurich, Zurich, Switzerland.
Dominik HaenniInstitute of Anatomy, University of Zurich, Zurich, Switzerland.
Claus D SchuhInstitute of Anatomy, University of Zurich, Zurich, Switzerland.
Ehud M LandauDepartment of Chemistry, University of Zurich, Zurich, Switzerland.
Andrew M HallInstitute of Anatomy, University of Zurich, Zurich, Switzerland.
University of Zurich · CHUniversity Hospital of Zurich · CHZurich University of Teacher Education · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kidney proximal tubules (PTs) contain a high density of mitochondria, which are required to generate ATP to power solute transport. Mitochondrial dysfunction is implicated in the pathogenesis of numerous kidney diseases. Damaged mitochondria are thought to produce excess reactive oxygen species (ROS), which can lead to oxidative stress and activation of cell death pathways. MitoQ is a mitochondrial targeted anti-oxidant that has shown promise in preclinical models of renal diseases. However, recent studies in nonkidney cells have suggested that MitoQ might also have adverse effects. Here, using a live imaging approach, and both in vitro and ex vivo models, we show that MitoQ induces rapid swelling and depolarization of mitochondria in PT cells, but these effects were not observed with SS-31, another targeted anti-oxidant. MitoQ consists of a lipophilic cation (Tetraphenylphosphonium [TPP]) joined to an anti-oxidant component (quinone) by a 10-carbon alkyl chain, which is thought to insert into the inner mitochondrial membrane (IMM). We found that mitochondrial swelling and depolarization was also induced by dodecyltriphenylphosphomium (DTPP), which consists of TPP and the alkyl chain, but not by TPP alone. Surprisingly, MitoQ-induced mitochondrial swelling occurred in the absence of a decrease in oxygen consumption rate. We also found that DTPP directly increased the permeability of artificial liposomes with a cardiolipin content similar to that of the IMM. In summary, MitoQ causes mitochondrial swelling and depolarization in PT cells by a mechanism unrelated to anti-oxidant activity, most likely because of increased IMM permeability due to insertion of the alkyl chain.

Indexed as

AnimalsAntioxidantsCells, CulturedKidney Tubules, ProximalMiceMitochondriaMitochondrial SwellingOpossumsOrganophosphorus CompoundsUbiquinoneAntioxidantsmitoquinoneOrganophosphorus CompoundsUbiquinoneAnti-oxidantkidneymitochondriaMitoQ

Identifiers

PMID29611340
PMCPMC5880956
OpenAlexW2795696541

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.