Proteomics Reveals that Methylmalonyl-CoA Mutase Modulates Cell Architecture and Increases Susceptibility to Stress.

International Journal of Molecular Sciences
Michele CostanzoMargherita Ruoppolo

Abstract

Methylmalonic acidemia (MMA) is a rare inborn error of metabolism caused by deficiency of the methylmalonyl-CoA mutase (MUT) enzyme. Downstream MUT deficiency, methylmalonic acid accumulates together with toxic metabolites from propionyl-CoA and other compounds upstream of the block in the enzyme pathway. The presentation is with life-threatening acidosis, respiratory distress, brain disturbance, hyperammonemia, and ketosis. Survivors develop poorly understood multi-organ damage, notably to the brain and kidneys. The HEK 293 cell line was engineered by CRISPR/Cas9 technology to knock out the MUT gene (MUT-KO). Shotgun label-free quantitative proteomics and bioinformatics analyses revealed potential damaging biological processes in MUT-deficient cells. MUT-KO induced alteration of cellular architecture and morphology, and ROS overproduction. We found the alteration of proteins involved in cytoskeleton and cell adhesion organization, cell trafficking, mitochondrial, and oxidative processes, as validated by the regulation of VIM, EXT2, SDC2, FN1, GLUL, and CHD1. Additionally, a cell model of MUT-rescuing was developed in order to control the specificity of MUT-KO effects. Globally, the proteomic landscape of MUT-KO suggests the ce...Continue Reading

References

Mar 17, 2005·Cellular and Molecular Life Sciences : CMLS·S Kölker, J G Okun
Sep 27, 2005·Molecular Genetics and Metabolism·R J Chandler, C P Venditti
Nov 4, 2005·The New England Journal of Medicine·Johannes HäberleHans G Koch
Jul 19, 2006·British Journal of Haematology·V Michael Whitehead
Jun 26, 2007·Cells, Tissues, Organs·Christine L ChafferElizabeth D Williams
Jul 31, 2007·Biochemistry·Jill K PatersonMichael M Gottesman
Dec 18, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Randy J ChandlerCharles P Venditti
Feb 4, 2011·Journal of Inherited Metabolic Disease·Ina KnerrK Michael Gibson
Apr 19, 2011·Molecular Genetics and Metabolism·Luciana HannibalDonald W Jacobsen
Nov 19, 2011·Cell Death and Differentiation·A Eisenberg-Lerner, A Kimchi
Dec 19, 2013·Nature Chemical Biology·Scott J Dixon, Brent R Stockwell
Apr 30, 2014·The Journal of Biological Chemistry·Toshiro MoroishiKeiichi I Nakayama
Feb 18, 2015·Molecular BioSystems·Emanuela ScolamieroMargherita Ruoppolo
Oct 10, 2015·Nucleic Acids Research·Sarah E CalvoVamsi K Mootha
Dec 18, 2015·Molecular BioSystems·Marianna CaterinoMargherita Ruoppolo
Jan 16, 2016·Microscopy Research and Technique·Hanae KataokaTakehiko Iijima
May 5, 2016·Nucleic Acids Research·Maxim V KuleshovAvi Ma'ayan
Sep 11, 2016·Clinical and Experimental Medicine·Guglielmo Rd VillaniMargherita Ruoppolo
Apr 7, 2017·Protoplasma·Renata Minuzzo HartmannNorma Possa Marroni
Sep 5, 2017·Kidney Diseases·Michele CostanzoMargherita Ruoppolo
Dec 23, 2017·KI Reports·Ahmed M Alkhunaizi, Nouriya Al-Sannaa
Mar 20, 2018·Scientific Reports·Margherita RuoppoloIlaria Campesi
Sep 12, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Antonia GiaccoPieter de Lange
Nov 6, 2018·Nucleic Acids Research·Yasset Perez-RiverolJuan Antonio Vizcaíno
Nov 16, 2018·International Journal of Molecular Sciences·Michele CostanzoMargherita Ruoppolo
Dec 14, 2018·Orphanet Journal of Rare Diseases·Johannes HäberleNicola Longo
Apr 2, 2019·Frontiers in Neuroscience·Maria Quiles Del Rey, Joseph D Mancias
May 24, 2019·Journal of Inherited Metabolic Disease·Hanneke A HaijesPeter M van Hasselt

❮ Previous
Next ❯

Citations

Feb 5, 2021·Scientific Reports·Marianna CaterinoGiuseppe Castaldo
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michele CostanzoMargherita Ruoppolo
Sep 21, 2021·Critical Reviews in Food Science and Nutrition·Elżbieta SupruniukAdrian Chabowski

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
gene knockout
Assay
X-ray
acetylation

Software Mentioned

Leica LAS AF
Andromeda
Rescue
Fiji J
Perseus
MetaboAnalyst
STRING
Human Phenotype Ontology
MUT
EnrichR

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.