Acetylation in Mitochondria Dynamics and Neurodegeneration

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Nov 27

PMID 34831252

Citations 7

Authors

Jaylyn Waddell

Aditi Banerjee

Tibor Kristian

Affiliations

Soon will be listed here.

Abstract

Mitochondria are a unique intracellular organelle due to their evolutionary origin and multifunctional role in overall cellular physiology and pathophysiology. To meet the specific spatial metabolic demands within the cell, mitochondria are actively moving, dividing, or fusing. This process of mitochondrial dynamics is fine-tuned by a specific group of proteins and their complex post-translational modifications. In this review, we discuss the mitochondrial dynamics regulatory enzymes, their adaptor proteins, and the effect of acetylation on the activity of fusion and fission machinery as a ubiquitous response to metabolic stresses. Further, we discuss the role of intracellular cytoskeleton structures and their post-translational modifications in the modulation of mitochondrial fusion and fission. Finally, we review the role of mitochondrial dynamics dysregulation in the pathophysiology of acute brain injury and the treatment strategies based on modulation of NAD-dependent deacetylation.

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References

Hammond J, Huang C, Kaech S, Jacobson C, Banker G, Verhey K . Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons. Mol Biol Cell. 2009; 21(4):572-83. PMC: 2820422. DOI: 10.1091/mbc.e09-01-0044. View

Nahhas F, Dryden S, Abrams J, Tainsky M . Mutations in SIRT2 deacetylase which regulate enzymatic activity but not its interaction with HDAC6 and tubulin. Mol Cell Biochem. 2007; 303(1-2):221-30. DOI: 10.1007/s11010-007-9478-6. View

Martin W, Hoffmeister M, Rotte C, Henze K . An overview of endosymbiotic models for the origins of eukaryotes, their ATP-producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle. Biol Chem. 2002; 382(11):1521-39. DOI: 10.1515/BC.2001.187. View

Perdiz D, Mackeh R, Pous C, Baillet A . The ins and outs of tubulin acetylation: more than just a post-translational modification?. Cell Signal. 2010; 23(5):763-71. DOI: 10.1016/j.cellsig.2010.10.014. View

Shida T, Cueva J, Xu Z, Goodman M, Nachury M . The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc Natl Acad Sci U S A. 2010; 107(50):21517-22. PMC: 3003046. DOI: 10.1073/pnas.1013728107. View

Martins de Brito O, Scorrano L . Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008; 456(7222):605-10. DOI: 10.1038/nature07534. View

Klimova N, Fearnow A, Long A, Kristian T . NAD precursor modulates post-ischemic mitochondrial fragmentation and reactive oxygen species generation via SIRT3 dependent mechanisms. Exp Neurol. 2019; 325:113144. PMC: 8328278. DOI: 10.1016/j.expneurol.2019.113144. View

Kamemura K, Ogawa M, Ohkubo S, Ohtsuka Y, Shitara Y, Komiya T . Depression of mitochondrial metabolism by downregulation of cytoplasmic deacetylase, HDAC6. FEBS Lett. 2012; 586(9):1379-83. DOI: 10.1016/j.febslet.2012.03.060. View

Kowaltowski A, de Souza-Pinto N, Castilho R, Vercesi A . Mitochondria and reactive oxygen species. Free Radic Biol Med. 2009; 47(4):333-43. DOI: 10.1016/j.freeradbiomed.2009.05.004. View

10.

Liszt G, Ford E, Kurtev M, Guarente L . Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem. 2005; 280(22):21313-20. DOI: 10.1074/jbc.M413296200. View

11.

Xu S, Cherok E, Das S, Li S, Roelofs B, Ge S . Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein. Mol Biol Cell. 2015; 27(2):349-59. PMC: 4713136. DOI: 10.1091/mbc.E15-09-0678. View

12.

Yoon S, Eom G . HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam Med J. 2016; 52(1):1-11. PMC: 4742605. DOI: 10.4068/cmj.2016.52.1.1. View

13.

Andreyev A, Kushnareva Y, Starkov A . Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc). 2005; 70(2):200-14. DOI: 10.1007/s10541-005-0102-7. View

14.

Zhang Q, Wu J, Wu R, Ma J, Du G, Jiao R . DJ-1 promotes the proteasomal degradation of Fis1: implications of DJ-1 in neuronal protection. Biochem J. 2012; 447(2):261-9. DOI: 10.1042/BJ20120598. View

15.

Kim S, Lu H, Alano C . Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron culture. PLoS One. 2011; 6(3):e14731. PMC: 3046953. DOI: 10.1371/journal.pone.0014731. View

16.

Satoh M, Hamamoto T, Seo N, Kagawa Y, Endo H . Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria. Biochem Biophys Res Commun. 2002; 300(2):482-93. DOI: 10.1016/s0006-291x(02)02874-7. View

17.

Nogales E, Wolf S, Downing K . Structure of the alpha beta tubulin dimer by electron crystallography. Nature. 1998; 391(6663):199-203. DOI: 10.1038/34465. View

18.

Filadi R, Greotti E, Pizzo P . Highlighting the endoplasmic reticulum-mitochondria connection: Focus on Mitofusin 2. Pharmacol Res. 2018; 128:42-51. DOI: 10.1016/j.phrs.2018.01.003. View

19.

Manor U, Bartholomew S, Golani G, Christenson E, Kozlov M, Higgs H . A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division. Elife. 2015; 4. PMC: 4574297. DOI: 10.7554/eLife.08828. View

20.

Spinelli J, Haigis M . The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018; 20(7):745-754. PMC: 6541229. DOI: 10.1038/s41556-018-0124-1. View