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Autophagy in Mitochondrial Quality Control

  • Rui Wang
  • Guanghui WangEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1206)

Abstract

Autophagy plays an important role in the renewal of cellular components, which function in energy production, metabolism, and clearance of damaged organelles. Both macroautophagy and microautophagy are involved in these processes. Although it was thought that nonselective macroautophagy is responsible for the clearance of damaged or old organelles, recent studies show that the clearance of cellular organelles depends on selective processes. Mitophagy is a process for selective degradation of mitochondria, which is well documented. The selective autophagy for other organelles includes endoplasmic reticulum autophagy (reticulophagy) and peroxisome autophagy (pexophagy). Autophagy is a routine pathway for cells to degrade unused proteins and damaged organelles in cells. Autophagy selectively removes dysfunctional cellular components but not damages the normally functioning organelles, to maintain the homeostasis of cells. In addition to the maintenance of the homeostasis of cells, autophagy clears the damaged organelles in disease or injury conditions to achieve cellular quality control. In some differentiated cells, such as red blood cells, some organelles are removed during the maturation, including mitochondria. The autophagy system can selectively clear the mitochondria and other organelles, which lead to the maturation of red blood cells. Dysfunction of autophagy impairs the clearance of damaged organelles, which results in injury of cells. In the maturation of red blood cells, failure to clear the cellular organelles by autophagy will disturb the normal differentiation of red blood cells, leading to a series of diseases such as anemia.

Keywords

Autophagy Mitochondria Mitophagy Fission Fusion PINK1 Parkin 

Abbreviations

AIM

Atg8-family interacting motif

Atg

Autophagy-related protein

CCCP

Carbonyl cyanide m-chlorophenyl hydrazone

Drp1

Dynamin-related protein 1

Fis1

Mitochondrial fission 1 protein

LC3

Microtubule-associated protein light chain 3

LIR

LC3-interacting region

MFN1/2

Mitofusin1/2

mtDNA

Mitochondrial DNA

OPA1

Optic atrophy 1

PE

Phosphatidylethanolamine

References

  1. Aerts L, Craessaerts K, De Strooper B et al (2015) PINK1 kinase catalytic activity is regulated by phosphorylation on serines 228 and 402. J Biol Chem 290:2798–2811CrossRefGoogle Scholar
  2. Clark IE, Dodson MW, Jiang C et al (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162–1166CrossRefGoogle Scholar
  3. El-Hattab AW, Suleiman J, Almannai M et al (2018) Mitochondrial dynamics: biological roles, molecular machinery, and related diseases. Mol Genet Metab 125:315–321CrossRefGoogle Scholar
  4. Greene JC, Whitworth AJ, Kuo I et al (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA 100:4078–4083CrossRefGoogle Scholar
  5. Kanki T, Wang K, Cao Y et al (2009) Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell 17:98–109CrossRefGoogle Scholar
  6. Liu L, Feng D, Chen G et al (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14:177–185CrossRefGoogle Scholar
  7. Narendra D, Tanaka A, Suen DF et al (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803CrossRefGoogle Scholar
  8. Narendra D, Tanaka A, Suen DF et al (2009) Parkin-induced mitophagy in the pathogenesis of Parkinson disease. Autophagy 5:706–708CrossRefGoogle Scholar
  9. Narendra DP, Jin SM, Tanaka A et al (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8:e1000298CrossRefGoogle Scholar
  10. Novak I, Kirkin V, McEwan DG et al (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11:45–51CrossRefGoogle Scholar
  11. Okamoto K, Kondo-Okamoto N, Ohsumi Y (2009) Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell 17:87–97CrossRefGoogle Scholar
  12. Ordureau A, Heo JM, Duda DM et al (2015) Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy. Proc Natl Acad Sci USA 112:6637–6642CrossRefGoogle Scholar
  13. Park J, Lee SB, Lee S et al (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441:1157–1161CrossRefGoogle Scholar
  14. Tilokani L, Nagashima S, Paupe V et al (2018) Mitochondrial dynamics: overview of molecular mechanisms. Essays Biochem 62:341–360CrossRefGoogle Scholar
  15. Vargas JNS, Wang C, Bunker E et al (2019) Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Molecular cellGoogle Scholar
  16. Wauer T, Simicek M, Schubert A et al (2015) Mechanism of phospho-ubiquitin-induced PARKIN activation. Nature 524:370–374CrossRefGoogle Scholar

Copyright information

© Science Press and Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases & Department of PharmacologyCollege of Pharmaceutical Sciences, Soochow UniversitySuzhouChina

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