Mitochondrial fragmentation in excitotoxicity requires ROCK activation

Cell Cycle
Alejandro Martorell-RieraFrancesc X Soriano

Abstract

Mitochondria morphology constantly changes through fission and fusion processes that regulate mitochondrial function, and it therefore plays a prominent role in cellular homeostasis. Cell death progression is associated with mitochondrial fission. Fission is mediated by the mainly cytoplasmic Drp1, which is activated by different post-translational modifications and recruited to mitochondria to perform its function. Our research and other studies have shown that in the early moments of excitotoxic insult Drp1 must be nitrosylated to mediate mitochondrial fragmentation in neurons. Nonetheless, mitochondrial fission is a multistep process in which filamentous actin assembly/disassembly and myosin-mediated mitochondrial constriction play prominent roles. Here we establish that in addition to nitric oxide production, excitotoxicity-induced mitochondrial fragmentation also requires activation of the actomyosin regulator ROCK. Although ROCK1 has been shown to phosphorylate and activate Drp1, experiments using phosphor-mutant forms of Drp1 in primary cortical neurons indicate that in excitotoxic conditions, ROCK does not act directly on Drp1 to mediate fission, but may act on the actomyosin complex. Thus, these data indicate that a wi...Continue Reading

References

Oct 24, 1998·The Journal of Cell Biology·E SmirnovaA M van der Bliek
Nov 13, 1999·Nature Cell Biology·W BleazardJ M Shaw
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Kirsi Riento, Anne J Ridley
May 3, 2005·Nature Reviews. Drug Discovery·Bernhard K MuellerNicole Teusch
Sep 28, 2005·The Journal of Cell Biology·Elena IngermanJodi Nunnari
Jul 29, 2006·The EMBO Journal·Mark J BarsoumElla Bossy-Wetzel
Mar 21, 2007·Nature Neuroscience·Maria M SemenovaMichael J Courtney
Feb 20, 2008·Current Opinion in Cell Biology·Michael F Olson
Oct 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·G M CereghettiL Scorrano
Dec 5, 2008·Nature·Olga Martins de Brito, Luca Scorrano
Jul 9, 2009·Physiological Reviews·Marc LiesaAntonio Zorzano
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Benedikt Westermann
Sep 3, 2011·Science·Jonathan R FriedmanGia K Voeltz
Mar 29, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Miguel A Perez-PinzonGary Fiskum
Aug 28, 2012·Neuron·Brian DuBoffMel B Feany
Sep 1, 2012·Science·Richard J Youle, Alexander M van der Bliek
Sep 5, 2012·EMBO Reports·Timothy ShuttHeidi M McBride
Jan 4, 2013·Molecular Biology of the Cell·Oliver C LosónDavid C Chan
Apr 23, 2013·Critical Reviews in Biochemistry and Molecular Biology·Alice V Schofield, Ora Bernard
Jan 3, 2014·Physiological Reviews·Laurent BlanchoinJulie Plastino
Feb 4, 2014·Current Biology : CB·Farida KorobovaHenry N Higgs
Aug 26, 2014·The EMBO Journal·Alejandro Martorell-RieraFrancesc X Soriano
Dec 31, 2014·The Journal of Cell Biology·Sunan LiMariusz Karbowski

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
GTPase
transfecting
transfection

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.

Related Papers

Free Radical Biology & Medicine
Chad A GallowayYisang Yoon
Biochimica Et Biophysica Acta
Hidenori OteraKatsuyoshi Mihara
Biochemical Society Transactions
Ralf J Braun, Benedikt Westermann
© 2021 Meta ULC. All rights reserved