KEGG   PATHWAY: dme04137
Entry
dme04137                    Pathway                                
Name
Mitophagy - animal - Drosophila melanogaster (fruit fly)
Description
Mitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process called reactive oxidative species (ROS) lead to mitochondrial dysfunction. If the damage is too excessive to be repaired, such mitochondria are selectively recognized and targeted for degradation by a specific mode of autophagy, termed mitophagy. The loss of the mitochondrial membrane potential can induce mitophagy, involving the kinase PINK1 and the E3 ligase Parkin. PINK1 serves as the sensor for the mitochondrial depolarization and recruits Parkin, followed by ubiquitin-dependent recruitment of mitophagy receptors. There are also several PINK1/Parkin-independent mitophagy pathways, in which a group of LIR-containing receptors are required in response to different stimuli. Mitophagy contributes to the maintenance of a healthy mitochondrial network and the prevention of programmed cell death.
Class
Cellular Processes; Transport and catabolism
Pathway map
dme04137  Mitophagy - animal
dme04137

Other DBs
GO: 0000422
Organism
Drosophila melanogaster (fruit fly) [GN:dme]
Gene
Dmel_CG10523  park; parkin, isoform B [KO:K04556] [EC:2.3.2.31]
Dmel_CG10761  CG10761; uncharacterized protein [KO:K10660] [EC:2.3.2.27]
Dmel_CG1134  Mul1; mitochondrial E3 ubiquitin protein ligase 1, isoform B [KO:K15688] [EC:2.3.2.27]
Dmel_CG11490  Tbc1d15-17; TBC1 domain family member 15/17, isoform B [KO:K20168]
Dmel_CG11624  Ubi-p63E; Ubiquitin-63E, isoform D [KO:K08770]
Dmel_CG1167  Ras64B; Ras oncogene at 64B [KO:K07830]
Dmel_CG11700  CG11700; uncharacterized protein [KO:K08770]
Dmel_CG11926  Mon1; monensin sensitivity 1 [KO:K20195]
Dmel_CG12157  Tom40; translocase of outer membrane 40, isoform C [KO:K11518]
Dmel_CG12334  Atg8b; Autophagy-related 8b, isoform B [KO:K08341]
Dmel_CG12511  CG12511; uncharacterized protein, isoform C [KO:K17986]
Dmel_CG13030  sinah; sina homologue [KO:K04506] [EC:2.3.2.27]
Dmel_CG13591  Ssl; suppressor of Stellate-like [KO:K03115]
Dmel_CG14690  [KO:K17770]
Dmel_CG14816  Pgam5; phosphoglycerate mutase 5, isoform A [KO:K15637] [EC:3.1.3.16]
Dmel_CG14980  Ccz1; Caffeine, calcium, zinc sensitivity 1 [KO:K27045]
Dmel_CG15081  Phb2; prohibitin 2, isoform D [KO:K17081]
Dmel_CG15224  CkIIbeta; casein kinase II beta subunit, isoform E [KO:K03115]
Dmel_CG15874  Pgam5-2; phosphoglycerate mutase 5-2 [KO:K15637] [EC:3.1.3.16]
Dmel_CG16781  CG16781; uncharacterized protein, isoform B [KO:K10660] [EC:2.3.2.27]
Dmel_CG17510  Fis1; Fission, mitochondrial 1, isoform C [KO:K17969]
Dmel_CG17520  CkIIalpha; casein kinase IIalpha, isoform D [KO:K03097] [EC:2.7.11.1]
Dmel_CG17991  CG17991; uncharacterized protein [KO:K10660] [EC:2.3.2.27]
Dmel_CG2087  PEK; pancreatic eIF-2alpha kinase, isoform A [KO:K08860] [EC:2.7.11.1]
Dmel_CG2275  Jra; Jun-related antigen, isoform A [KO:K04448]
Dmel_CG2331  TER94; transitional endoplasmic reticulum 94, isoform A [KO:K13525]
Dmel_CG2615  IKKepsilon; I-kappaB kinase epsilon, isoform C [KO:K05410] [EC:2.7.11.10]
Dmel_CG2960  RpL40; ribosomal protein L40, isoform B [KO:K02927]
Dmel_CG3016  Usp30; ubiquitin specific protease 30, isoform B [KO:K11851] [EC:3.4.19.12]
Dmel_CG3143  foxo; forkhead box, sub-group O, isoform C [KO:K09408]
Dmel_CG32616  Ste12DOR; stellate 12D orphon [KO:K03115]
Dmel_CG32672  Atg8a; Autophagy-related 8a, isoform B [KO:K08341]
Dmel_CG32744  Ubi-p5E; Ubiquitin-5E, isoform B [KO:K08770]
Dmel_CG33236  [KO:K03115]
Dmel_CG33237  [KO:K03115]
Dmel_CG33238  [KO:K03115]
Dmel_CG33239  [KO:K03115]
Dmel_CG33240  [KO:K03115]
Dmel_CG33241  [KO:K03115]
Dmel_CG33242  [KO:K03115]
Dmel_CG33243  [KO:K03115]
Dmel_CG33244  [KO:K03115]
Dmel_CG33245  [KO:K03115]
Dmel_CG33246  [KO:K03115]
Dmel_CG33247  [KO:K03115]
Dmel_CG3615  Atg9; Autophagy-related 9, isoform B [KO:K17907]
Dmel_CG3664  Rab5; Rab5, isoform G [KO:K07888]
Dmel_CG3869  Marf; mitochondrial assembly regulatory factor, isoform C [KO:K06030] [EC:3.6.5.-]
Dmel_CG40635  CG40635; uncharacterized protein [KO:K03115]
Dmel_CG42398  [KO:K03115]
Dmel_CG45051  sima; uncharacterized protein [KO:K08268]
Dmel_CG4568  fzo; fuzzy onions [KO:K06030] [EC:3.6.5.-]
Dmel_CG4943  Smurf; SMAD specific E3 ubiquitin protein ligase, isoform B [KO:K04678] [EC:2.3.2.26]
Dmel_CG5059  BNIP3; BNIP3, isoform E [KO:K15464]
Dmel_CG5271  RpS27A; ribosomal protein S27A [KO:K02977]
Dmel_CG5410  Miro; mitochondrial Rho, isoform D [KO:K07870] [EC:3.6.5.-]
Dmel_CG5429  Atg6; Autophagy-related 6 [KO:K08334]
Dmel_CG5482  zda; zonda, isoform B [KO:K09574] [EC:5.2.1.8]
Dmel_CG5659  ari-1; ariadne 1, isoform D [KO:K11968] [EC:2.3.2.31]
Dmel_CG5662  CG5662; uncharacterized protein, isoform B [KO:K17776]
Dmel_CG5676  CG5676; uncharacterized protein [KO:K17986]
Dmel_CG5680  bsk; basket, isoform F [KO:K04440] [EC:2.7.11.24]
Dmel_CG5798  Usp8; ubiquitin specific protease 8, isoform B [KO:K11839] [EC:3.4.19.12]
Dmel_CG5915  Rab7; Rab7, isoform B [KO:K07897]
Dmel_CG6756  Tom70; translocase of outer membrane 70, isoform A [KO:K17768]
Dmel_CG7524  Src64B; Src oncogene at 64B, isoform D [KO:K05704] [EC:2.7.10.2]
Dmel_CG7639  CG7639; uncharacterized protein [KO:K07277]
Dmel_CG7654  Tom20; translocase of outer membrane 20, isoform B [KO:K17770]
Dmel_CG8004  CG8004; uncharacterized protein [KO:K17776]
Dmel_CG8184  HUWE1; HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1, isoform H [KO:K10592] [EC:2.3.2.26]
Dmel_CG8226  Tom7; translocase of outer membrane 7, isoform B [KO:K17771]
Dmel_CG8330  [KO:K11518]
Dmel_CG8479  Opa1; optic atrophy 1, isoform C [KO:K17079] [EC:3.6.5.5]
Dmel_CG8669  crc; cryptocephal, isoform E [KO:K04374]
Dmel_CG8914  CkIIbeta2; casein kinase II beta2 subunit [KO:K03115]
Dmel_CG9139  Rabex-5; Rabaptin-5-associated exchange factor for Rab5 [KO:K20131]
Dmel_CG9375  Ras85D; Ras oncogene at 85D [KO:K07827]
Dmel_CG9393  CG9393; uncharacterized protein, isoform A [KO:K17776]
Dmel_CG9855  CG9855; uncharacterized protein, isoform C [KO:K10660] [EC:2.3.2.27]
Dmel_CG9946  eIF2alpha; eukaryotic translation initiation factor 2 subunit alpha, isoform B [KO:K03237]
Dmel_CG9949  sina; seven in absentia, isoform C [KO:K04506] [EC:2.3.2.27]
Compound
C00035  GDP
C00044  GTP
Reference
  Authors
Pickrell AM, Youle RJ
  Title
The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
  Journal
Neuron 85:257-73 (2015)
DOI:10.1016/j.neuron.2014.12.007
Reference
  Authors
Durcan TM, Fon EA
  Title
The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
  Journal
Genes Dev 29:989-99 (2015)
DOI:10.1101/gad.262758.115
Reference
  Authors
Shirihai OS, Song M, Dorn GW 2nd
  Title
How mitochondrial dynamism orchestrates mitophagy.
  Journal
Circ Res 116:1835-49 (2015)
DOI:10.1161/CIRCRESAHA.116.306374
Reference
  Authors
Hamacher-Brady A, Brady NR
  Title
Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
  Journal
Cell Mol Life Sci 73:775-95 (2016)
DOI:10.1007/s00018-015-2087-8
Reference
  Authors
Yamano K, Matsuda N, Tanaka K
  Title
The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation.
  Journal
EMBO Rep 17:300-16 (2016)
DOI:10.15252/embr.201541486
Reference
  Authors
Yamaguchi O, Murakawa T, Nishida K, Otsu K
  Title
Receptor-mediated mitophagy.
  Journal
J Mol Cell Cardiol 95:50-6 (2016)
DOI:10.1016/j.yjmcc.2016.03.010
Reference
  Authors
Roberts RF, Tang MY, Fon EA, Durcan TM
  Title
Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles.
  Journal
Int J Biochem Cell Biol 79:427-436 (2016)
DOI:10.1016/j.biocel.2016.07.020
Reference
  Authors
Arena G, Valente EM
  Title
PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease.
  Journal
J Pathol 241:251-263 (2017)
DOI:10.1002/path.4815
Related
pathway
dme04140  Autophagy - animal
KO pathway
ko04137   

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