The valosin-containing protein protects the heart against pathological Ca2+ overload by modulating Ca2+ uptake proteins

Toxicological Sciences : an Official Journal of the Society of Toxicology
Shaunrick StollHongyu Qiu

Abstract

Stress-induced mitochondrial calcium (Ca2+) overload is a key cellular toxic effectors and a trigger of cardiomyocyte death during cardiac ischemic injury through the opening of mitochondrial permeability transition pore (mPTP). We previously found that the valosin-containing protein (VCP), an ATPase-associated protein, protects cardiomyocytes against stress-induced death and also inhibits mPTP opening in vitro. However, the underlying molecular mechanisms are not fully understood. Here, we tested our hypothesis that VCP acts as a novel regulator of mitochondrial Ca2+ uptake proteins and resists cardiac mitochondrial Ca2+ overload by modulating mitochondrial Ca2+ homeostasis. By using a cardiac-specific transgenic (TG) mouse model in which VCP is overexpressed by 3.5 folds in the heart compared to the wild type (WT) mouse, we found that, under the pathological extra-mitochondrial Ca2+ overload, Ca2+ entry into cardiac mitochondria was reduced in VCP TG mice compared to their little-matched WT mice, subsequently preventing mPTP opening and ATP depletion under the Ca2+ challenge. Mechanistically, overexpression of VCP in the heart resulted in post-translational protein degradation of the mitochondrial Ca2+ uptake protein 1 (MICU1...Continue Reading

References

Jan 5, 2002·Molecular and Cellular Biology·Efrat RabinovichShoshana Bar-Nun
Apr 3, 2002·Japanese Journal of Cancer Research : Gann·Tatsuya AsaiKatsuyuki Aozasa
Feb 1, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shinji YamamotoKatsuyuki Aozasa
May 8, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuichi TsujimotoKatsuyuki Aozasa
Nov 26, 2008·The Journal of Cell Biology·Derek NarendraRichard J Youle
Jan 27, 2009·Biochimica Et Biophysica Acta·Andrew P Halestrap, Philippe Pasdois
Feb 27, 2009·Basic Research in Cardiology·Christopher P Baines
Jun 9, 2009·Cardiovascular Research·David Garcia-DoradoHans Michael Piper
Jan 13, 2010·Basic Research in Cardiology·Gerd HeuschRainer Schulz
Jan 19, 2010·Biochimica Et Biophysica Acta·Jaime Santo-Domingo, Nicolas Demaurex
Dec 2, 2010·Molecular Biology of the Cell·Shan XuMariusz Karbowski
Sep 21, 2011·The Journal of Biological Chemistry·Tiffany T NguyenElizabeth Murphy
Nov 8, 2011·Methods in Molecular Biology·Renee WongElizabeth Murphy
Apr 17, 2012·Cell Calcium·Andrei I TarasovGuy A Rutter
May 19, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Klitos KonstantinidisRichard N Kitsis
Jan 3, 2013·The Journal of Clinical Investigation·Derek J Hausenloy, Derek M Yellon
Apr 23, 2013·Acta Pharmacologica Sinica·Fang YangChun-feng Liu
Dec 20, 2013·The Biochemical Journal·Joseph R Tran, Jeffrey L Brodsky
Aug 26, 2014·Journal of Cell Science·Hemmo Meyer, Conrad C Weihl
Dec 3, 2014·Journal of Molecular and Cellular Cardiology·Sang-Bing OngDerek J Hausenloy
Jan 23, 2015·Neuron·Alicia M Pickrell, Richard J Youle
Apr 22, 2015·Biochimica Et Biophysica Acta·Diego De StefaniRosario Rizzuto
May 20, 2015·Basic Research in Cardiology·Christoph KoentgesHeiko Bugger
May 23, 2015·Circulation Research·Toren FinkelElizabeth Murphy
Jul 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Gaetano SantulliAndrew R Marks
Feb 24, 2016·Biochimica Et Biophysica Acta·Jessica Matesanz-IsabelJavier Alvarez
Dec 20, 2016·The Journal of Physiology·Jennifer Q Kwong
May 2, 2017·Developmental Biology·María José Pérez, Rodrigo A Quintanilla
Nov 24, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ning ZhouHongyu Qiu
Jul 7, 2018·Cell Calcium·Neeharika NemaniMuniswamy Madesh
Sep 23, 2018·Scientific Reports·Alessandra MatteucciTito Calì
May 24, 2019·Frontiers in Molecular Biosciences·Ryo Motosugi, Shigeo Murata

❮ Previous
Next ❯

Citations

Sep 24, 2020·International Journal of Molecular Sciences·Mafalda Escobar-Henriques, Vincent Anton
Oct 22, 2020·International Journal of Molecular Sciences·Lo Lai, Hongyu Qiu
Jan 14, 2021·Biochemical Society Transactions·Hongyang ShuDao Wen Wang
May 1, 2021·International Journal of Molecular Sciences·Xiaonan SunHongyu Qiu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.