Autophagy as a Cellular Stress Response Mechanism in the Nervous System. Issue 8 (3rd April 2020)

• Record Type: Journal Article
• Authors: Peker, Nesibe; Gozuacik, Devrim
• Is Part Of: Journal of molecular biology. Volume 432:Issue 8(2020)
• Page Start: 2560
• Page End: 2588
• Publication Date: 2020-04-03
• Subjects: autophagy -- cellular stress -- nervous system -- neuron -- neurodegenerative disease; Aβ amyloid beta -- AD alzheimer's disease -- AMBRA1 autophagy and beclin 1 regulator 1 -- AMPK 5′ AMP-activated protein kinase -- APP amyloid precursor protein -- ASK1 apoptosis signal–regulating kinase 1 -- ATF activating transcription factor -- ATG autophagy-related gene -- BCL 2 B-cell lymphoma 2 -- BER base-excision repair -- BIP binding immunoglobulin protein -- BNIP3L/NIX BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like -- CaMKKβ Ca2+-calmodulin-dependent kinase kinase-β -- CAT catalase -- CHOP C/EBP homologous protein -- CMA chaperone-mediated autophagy -- DAPK death-associated protein kinase -- DDR DNA damage response -- DUB deubiquitinating enzyme -- eIF2α eukaryotic initiation factor 2 alpha -- ERAD ER-associated degradation -- FOXO forkhead box O -- FRDA friedreich ataxia -- GAP GTPase-activating protein -- GEF guanine nucleotide exchange factor -- GP78 glycoprotein 78 -- GPx glutathione peroxidase -- GSH glutathione -- HD Huntington's disease -- HR homologous recombination -- HTT Huntingtin protein -- IP3 inositol 1, 4, 5-trisphosphate -- IP3R inositol 1, 4, 5-trisphosphate receptor -- IRE1α inositol-requiring enzyme 1 α -- JNK c-Jun N-terminal kinase -- LAMP1 lysosomal-associated membrane protein 1 -- LC3 microtubule-associated protein 1A/1B-light chain 3 -- LIR LC3-interacting region -- MARCH5 membrane associated ring–CH–type finger 5 -- MFN mitofusin -- mHTT mutant Huntingtin protein -- MITF microphthalmia-associated transcription factor -- MRP1 multidrug resistance-associated protein 1 -- MPP mitochondrial processing peptidase -- MPP+ 1-methyl-4-phenylpyridinium -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- mTOR mammalian target of rapamycin -- mTORC mammalian target of rapamycin complex -- MUL1 mitochondrial ubiquitin ligase 1 -- NDP52 nuclear domain 10 protein -- NER nucleotide excision repair -- NHEJ nonhomologous end joining -- NRF2 nuclear factor erythroid 2-related factor 2 -- OMM outer mitochondrial membrane -- OPTN optineurin -- PARL presenilin-associated rhomboid-like protein -- PERK PKR-like endoplasmic reticulum kinase -- PD Parkinson's disease -- PE phosphatidylethanolamine -- PINK1 PTEN-induced kinase 1 -- PI3P phosphatidylinositol 3-phosphate -- RAG recombination activating gene -- ROS reactive oxygen species -- SOCS2 suppressor of cytokine signalling 2 -- SOD superoxide dismutase -- TFE3 transcription factor E3 -- TFEB transcription Factor EB -- TRAF TNF-R-associated factor -- Trx thioredoxin -- TSC tuberous sclerosis protein -- Ub ubiquitin -- ULK1 Unc-51 like autophagy activating kinase 1 -- UPR unfolded protein response -- UPS ubiquitin proteasome system -- WAC WW domain containing adaptor with coiled-coil -- WIPI WD repeat domain, phosphoinositide interacting -- XBP1 X-Box binding protein 1 -- 8-oxo-dG 8-oxo-deoxy guanosine -- ΔΨm mitochondrial membrane potential; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.01.017
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Cells of an organism face with various types of insults during their lifetime. Exposure to toxins, metabolic problems, ischaemia/reperfusion, physical trauma, genetic diseases, neurodegenerative diseases are among the conditions that trigger cellular stress responses. In this context, autophagy is one of the mechanisms that supports cell survival under stressful conditions. Autophagic vesicle engulfs the cargo and transports it to lysosome for degradation and turnover. As such, autophagy eliminates abnormal proteins, clears damaged organelles, limits oxidative stress and helps to improve metabolic balance. Nervous system cells and particularly postmitotic neurons are highly sensitive to a spectrum of insults, and autophagy emerges as one of the key stress response mechanism, ensuring health and survival of these vulnerable cell types. In this review, we will overview mechanisms through which cells cope with stress, and how these stress responses regulate autophagy, with a special focus on the nervous system. Graphical abstract: Image 1 Highlights: Stress factors activate cellular stress response mechanisms in cells. Postmitotic cells in the nervous system are sensitive to cellular stress. Autophagy is a main stress response mechanism in nervous system cells. Autophagy clears damaged proteins and organelles, and maintains metabolic balance. Therapeutic strategies targeting autophagy may alleviate neurodegenerative diseases.