Evidence map›Paper›PMID 28442264›Full record

ArticleBiochimica et biophysica acta. Bioenergetics2017

Mitochondrial LON protease-dependent degradation of cytochrome c oxidase subunits under hypoxia and myocardial ischemia.

Naresh B V Sepuri, Rajesh Angireddy, Satish Srinivasan, Manti Guha, Joseph Spear, Bin Lu, Hindupur K Anandatheerthavarada, Carolyn K Suzuki, Narayan G Avadhani

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta. Bioenergetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 46 citations in OpenAlex.

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  16. Quality control of the mitochondrial proteome.Nature reviews. Molecular cell biology · 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

9 authors at 2 institutions in 1 country.

Naresh B V SepuriDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA.
Rajesh AngireddyDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA.
Satish SrinivasanDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA.
Manti GuhaDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA.
Joseph SpearDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA.
Bin LuDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers The State University, New Jersey Medical School, 225 Warren Street, Newark, NJ 17103-3535, USA.
Hindupur K AnandatheerthavaradaDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA.
Carolyn K SuzukiDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers The State University, New Jersey Medical School, 225 Warren Street, Newark, NJ 17103-3535, USA.
Narayan G AvadhaniDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA. Electronic address: narayan@vet.upenn.edu.
University of Pennsylvania · USRutgers, The State University of New Jersey · US

Funding

Role of Mitochondria-Targeted CYP2D6 in Chemical ToxicityR01GM034883 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI AVADHANI, NARAYAN G · 1985 to 2018
$6.1M
Ahr and OsteoporosisR01AR067066 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AVADHANI, NARAYAN G, ZAIDI, MONE · 2014 to 2018
$3.3M
CYP2E1 Mediated Mitochondrial Injury and Cell Damage in Alcohol Liver DiseaseR01AA022986 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI AVADHANI, NARAYAN G, KALYANARAMAN, BALARAMAN · 2015 to 2019
$2.6M
NIAAA NIH HHS R01 AA022986NIAMS NIH HHS R01 AR067066NIGMS NIH HHS R01 GM034883
6 · The paper itself

Abstract

The mitochondrial ATP dependent matrix protease, Lon, is involved in the maintenance of mitochondrial DNA nucleoids and degradation of abnormal or misfolded proteins. The Lon protease regulates mitochondrial Tfam (mitochondrial transcription factor A) level and thus modulates mitochondrial DNA (mtDNA) content. We have previously shown that hypoxic stress induces the PKA-dependent phosphorylation of cytochrome c oxidase (CcO) subunits I, IVi1, and Vb and a time-dependent reduction of these subunits in RAW 264.7 murine macrophages subjected to hypoxia and rabbit hearts subjected to ischemia/reperfusion. Here, we show that Lon is involved in the preferential turnover of phosphorylated CcO subunits under hypoxic/ischemic stress. Induction of Lon protease occurs at 6 to 12 h of hypoxia and this increase coincides with lower CcO subunit contents. Over-expression of flag-tagged wild type and phosphorylation site mutant Vb and IVi1 subunits (S40A and T52A, respectively) caused marked degradation of wild type protein under hypoxia while the mutant proteins were relatively resistant. Furthermore, the recombinant purified Lon protease degraded the phosphorylated IVi1 and Vb subunits, while the phosphorylation-site mutant proteins were resistant to degradation. 3D structural modeling shows that the phosphorylation sites are exposed to the matrix compartment, accessible to matrix PKA and Lon protease. Hypoxic stress did not alter CcO subunit levels in Lon depleted cells, confirming its role in CcO turnover. Our results therefore suggest that Lon preferentially degrades the phosphorylated subunits of CcO and plays a role in the regulation of CcO activity in hypoxia and ischemia/reperfusion injury.

Indexed as

AnimalsATP-Dependent ProteasesCell HypoxiaCyclic AMP-Dependent Protein KinasesElectron Transport Complex IVHumansMaleMiceMitochondria, HeartMitochondrial ProteinsModels, MolecularMyocardial IschemiaPhosphorylationProtein ConformationProtein Processing, Post-TranslationalProtein SubunitsATP-Dependent ProteasesCyclic AMP-Dependent Protein KinasesElectron Transport Complex IVLONP1 protein, humanLONP1 protein, mouseMitochondrial ProteinsProtein SubunitsRecombinant ProteinsRNA, Small Interfering3D modelingCcO subunitsHeart ischemiaHypoxiaMitochondrial LONPKA dependent phosphorylation

Identifiers

PMID28442264
PMCPMC5507603
OpenAlexW2606866555

What OpenQuestion holds

Textmetadata
LicenceTDM
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.