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Autophagy—Cell Survival and Death

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Autophagy: Biology and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1206))

Abstract

Autophagy, which is one of the most important ways to maintain cell homeostasis plays an important regulatory role in cell survival and death. Currently, it is agreed that autophagy promotes or inhibits cell death depending on the internal and external environment and cell type. On the one hand, under normal nutritional conditions autophagy regulates cell survival by energy sensing through the main energy sensing cascade kinases. On the other hand, autophagy regulates the process of cell death. mTOR, Beclin 1, caspases, FLIPs, DAPK, and Tp53 play important regulatory roles in autophagy and apoptosis highlighting the crosstalk between the mechanisms underlying the two death modes. However, energy deficiency caused by PARP1 over-activation and DAPK-PKD pathway activation induces necrosis and autophagy, highlighting the interaction between the two pathways. In addition, autophagy regulates cell death through epigenetic regulation such as histone modification. More investigations on the relationship between autophagy and cell death is ongoing. In the future, there will be more challenges in the study of the relationship between autophagy and cell survival and death. As research increasingly focuses on cell death, the relationship between autophagy and existing and newly discovered cell death types is likely to become more complex. The elucidation of the regulatory role of autophagy in cell survival and death requires more research. Some research results are likely to provide hot topics for further investigations on diseases related to cell death disorders and an experimental basis for the targeted regulation of autophagy for specific treatment of diseases.

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Abbreviations

ACD:

Accidental cell death

AIF:

Apoptosis-inducing factor

AMPK:

Adenosine 5′-monophosphate (AMP)-activated protein kinase

Bruce:

BIR-containing ubiquitin-conjugating enzyme

CMA:

Chaperone-mediated autophagy

CSE:

Cigarette smoke extract

DISC:

Fas-dependent death-inducing signaling complex

DRAM:

Damage-regulated autophagy modulator

FADD:

FAS-associated death domain

FAK:

Focal adhesion kinase

FLICE:

FADD-like interleukin-1 beta-converting enzyme

FLIP:

Flice inhibitory protein

GABARAP-L1:

Γ-aminobutyric acid receptor-associated protein-like 1

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

HMGB1:

High mobility group B1

IAPs:

Inhibitor of apoptosis proteins

IFN:

Interferon

IL3:

Interleukin 3

IMS:

Intermembrane space

LAMP2A:

Lysosome-associated membrane protein type 2A

MEF2D:

Myocyte enhancer factor 2D

MEFs:

Mouse embryonic fibroblasts

MFN1:

Mitofusin 1

MOMP:

Mitochondrial outer membrane permeabilization

mTOR:

Mammalian target of rapamycin

NBR1:

The neighbor of BRCA1 gene 1

NCCD:

Nomenclature Committee on Cell Death

PARKIN:

Parkinson’s disease protein

PINK1:

PTEN-induced putative kinase 1

PKA:

Protein kinase A

PKD:

Protein kinase D1

PTP:

Permeability transition pore

RCD:

Regulated cell death

RIP1:

Kinases receptor-interacting protein 1

ROS:

Reactive oxygen species

SMAC:

Second mitochondria-derived activator of caspase

SQSTM1:

Sequestosome 1, p62

TNF:

Tumour necrosis factor

TNF/NGF:

Tumor necrosis factor/nerve growth factor

TRAIL:

TNF-related apoptosis-inducing ligand

VDAC1:

Voltage-dependent anion-selective channel 1

VMP1:

Vacuole membrane protein

References

  • Chang CR, Blackstone C (2007) Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J Biol Chem 282(30):21583–21587

    Article  CAS  Google Scholar 

  • Chen Z, Nie SD, Qu ML et al (2018) The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes. Cell Death Dis 9(7):771

    Article  Google Scholar 

  • Egan DF, Shackelford DB, Mihaylova MM et al (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331(6016):456–461

    Article  CAS  Google Scholar 

  • Eisenberg-Lerner A, Kimchi A (2012) PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk. Cell Death Differ 19(5):788–797

    Article  CAS  Google Scholar 

  • Fernandez AF, Sebti S, Wei YJ et al (2018) Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice. Nature 558(7708):136–140

    Article  CAS  Google Scholar 

  • Fullgrabe J, Heldring N, Hermanson O et al (2014) Cracking the survival code autophagy-related histone modifications. Autophagy 10(4):556–561

    Article  Google Scholar 

  • Galluzzi L, Vitale I, Aaronson SA et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25(3):486–541

    Article  Google Scholar 

  • Garcia-Prat L, Martinez-Vicente M, Perdiguero E et al (2016) Autophagy maintains stemness by preventing senescence. Nature 529(7584):37–42

    Article  CAS  Google Scholar 

  • Goodall ML, Fitzwalter BE, Zahedi S et al (2016) The autophagy machinery controls cell death switching between apoptosis and necroptosis. Dev Cell 37(4):337–349

    Article  CAS  Google Scholar 

  • Gozuacik D, Bialik S, Raveh T et al (2008) DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death. Cell Death Differ 15(12):1875–1886

    Article  CAS  Google Scholar 

  • Ichimura Y, Waguri S, Sou Y et al (2013) Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell 51(5):618–631

    Article  CAS  Google Scholar 

  • Imagawa Y, Saitoh T, Tsujimoto Y (2016) Vital staining for cell death identifies Atg9a-dependent necrosis in developmental bone formation in mouse. Nat Commun 7:13391

    Article  CAS  Google Scholar 

  • Jangamreddy JR, Los MJ (2012) Mitoptosis, a novel mitochondrial death mechanism leading predominantly to activation of autophagy. Hepat Mon 12(8):e6159

    Article  Google Scholar 

  • Lee JS, Li QL, Lee JY et al (2009) FLIP-mediated autophagy regulation in cell death control. Nat Cell Biol 11(11):1355–1362

    Article  CAS  Google Scholar 

  • Luo S, Rubinsztein DC (2010) Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL. Cell Death Differ 17(2):268–277

    Article  CAS  Google Scholar 

  • Mihaylova MM, Shaw RJ (2011) The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol 13(9):1016–1023

    Article  CAS  Google Scholar 

  • Pan HH, Yan Y, Liu CY et al (2017) The role of ZKSCAN3 in the transcriptional regulation of autophagy. Autophagy 13(7):1235–1238

    Article  CAS  Google Scholar 

  • Pattingre S, Tassa A, Qu XP et al (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122(6):927–939

    Article  CAS  Google Scholar 

  • Poillet-Perez L, Xie XQ, Zhan L et al (2018) Autophagy maintains tumour growth through circulating arginine. Nature 563(7732):569–573

    Article  CAS  Google Scholar 

  • Sun L, Meng ZY, Zhu YF et al (2018) TM9SF4 is a novel factor promoting autophagic flux under amino acid starvation. Cell Death Differ 25(2):368–379

    Article  CAS  Google Scholar 

  • Tan MJ, Luo H, Lee S et al (2011) Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146(6):1015–1027

    Article  Google Scholar 

  • Yamaguchi T, Suzuki T, Sato T et al (2018) The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function. Sci Signal 11(516):eaan3638

    Article  Google Scholar 

  • Yu L, McPhee CK, Zheng LX et al (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465(7300):942–946

    Article  CAS  Google Scholar 

  • Zaffagnini G, Savova A, Danieli A et al (2018) p62 filaments capture and present ubiquitinated cargos for autophagy. EMBO J 37(5):e98308

    Article  Google Scholar 

  • Zhang GM, Wang Z, Du Z et al (2018) mTOR regulates phase separation of PGL granules to modulate their autophagic degradation. Cell 174(6):1492–1506

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China

    Xiaojie Yan, Ruimin Zhou & Zhenyi Ma

Authors
  1. Xiaojie Yan
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  2. Ruimin Zhou
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  3. Zhenyi Ma
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Correspondence to Zhenyi Ma .

Editor information

Editors and Affiliations

  1. Jiangsu Key Laboratory of Neuropsychiatric Diseases, Department of Pharmacology and Laboratory of Aging and Nervous Diseases, College of Pharmaceutical Sciences of Soochow University, Suzhou, China

    Zheng-Hong Qin

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Yan, X., Zhou, R., Ma, Z. (2019). Autophagy—Cell Survival and Death. In: Qin, ZH. (eds) Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1206. Springer, Singapore. https://doi.org/10.1007/978-981-15-0602-4_29

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