KEGG   PATHWAY: uar04137
Entry
uar04137                    Pathway                                
Name
Mitophagy - animal - Ursus americanus (American black bear)
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
uar04137  Mitophagy - animal
uar04137

Other DBs
GO: 0000422
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123799572  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
123782135  PINK1; serine/threonine-protein kinase PINK1, mitochondrial [KO:K05688] [EC:2.7.11.1]
123795178  mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
123789181  TOMM7; mitochondrial import receptor subunit TOM7 homolog isoform X1 [KO:K17771]
123802247  TOMM40; mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
123783567  TOMM40L; mitochondrial import receptor subunit TOM40B [KO:K11518]
123800663  TOMM20L; TOMM20-like protein 1 [KO:K17770]
123782919  TOMM20; mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
123784109  TOMM70; mitochondrial import receptor subunit TOM70 [KO:K17768]
123797535  PRKN; E3 ubiquitin-protein ligase parkin isoform X1 [KO:K04556] [EC:2.3.2.31]
123800300  MARCHF5; E3 ubiquitin-protein ligase MARCHF5 [KO:K10660] [EC:2.3.2.27]
123796334  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
123802558  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
123803252  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
123798420  AMFR; E3 ubiquitin-protein ligase AMFR [KO:K10636] [EC:2.3.2.36]
123782332  MUL1; mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
123793527  HUWE1; E3 ubiquitin-protein ligase HUWE1 isoform X1 [KO:K10592] [EC:2.3.2.26]
123797289  E3 ubiquitin-protein ligase SIAH1-like [KO:K04506] [EC:2.3.2.27]
123798384  SIAH1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
123790708  ARIH1; E3 ubiquitin-protein ligase ARIH1 [KO:K11968] [EC:2.3.2.31]
123786410  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
123779618  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
123776840  RHOT1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
123783258  RHOT2; mitochondrial Rho GTPase 2 isoform X1 [KO:K07871] [EC:3.6.5.-]
123779925  UBA52; ubiquitin-60S ribosomal protein L40 [KO:K02927]
123795660  ubiquitin-60S ribosomal protein L40 [KO:K02927]
123785937  RPS27A; ubiquitin-40S ribosomal protein S27a [KO:K02977]
123779762  UBB; polyubiquitin-B [KO:K04551]
123798227  LOW QUALITY PROTEIN: polyubiquitin-like [KO:K04551]
123780227  UBC; polyubiquitin-C [KO:K08770]
123789129  TAX1BP1; tax1-binding protein 1 isoform X1 [KO:K21347]
123790491  SQSTM1; sequestosome-1 [KO:K14381]
123802839  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 [KO:K21348]
123789989  OPTN; optineurin isoform X1 [KO:K19946]
123781965  NBR1; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
123787173  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
123792166  LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor-associated protein [KO:K08341]
123781641  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
123791319  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
123790991  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
123798215  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
123791286  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
123776674  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
123781873  BECN1; beclin-1 isoform X1 [KO:K08334]
123790998  BECN2; beclin-2 [KO:K08334]
123801789  USP8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
123787187  USP15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
123788220  USP30; ubiquitin carboxyl-terminal hydrolase 30 isoform X1 [KO:K11851] [EC:3.4.19.12]
123798690  BCL2L1; bcl-2-like protein 1 [KO:K04570]
123803885  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
123798458  CSNK2A2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
123798805  CSNK2A1; casein kinase II subunit alpha isoform X1 [KO:K03097] [EC:2.7.11.1]
123791006  CSNK2B; casein kinase II subunit beta [KO:K03115]
123796968  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
123803317  ULK1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
123794549  FUNDC1; FUN14 domain-containing protein 1 [KO:K17986]
123800038  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
123777393  BNIP3L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like isoform X1 [KO:K15465]
123778006  BCL2L13; bcl-2-like protein 13 isoform X1 [KO:K15485]
123779960  FKBP8; peptidyl-prolyl cis-trans isomerase FKBP8 isoform X1 [KO:K09574] [EC:5.2.1.8]
123780525  SAMM50; sorting and assembly machinery component 50 homolog [KO:K07277]
123781537  PHB2; LOW QUALITY PROTEIN: prohibitin-2 [KO:K17081]
123792650  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
123798072  MTX2; metaxin-2 [KO:K17776]
123783428  MTX1; metaxin-1 [KO:K17776]
123791531  MTX3; metaxin-3 isoform X1 [KO:K17776]
123799721  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
123800625  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
123780649  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123800287  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123788054  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123790496  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123795376  JUN; transcription factor AP-1 [KO:K04448]
123778302  RELA; transcription factor p65 [KO:K04735]
123775506  HRAS; GTPase HRas isoform X1 [KO:K02833]
123801699  KRAS; GTPase KRas isoform X1 [KO:K07827]
123795037  NRAS; GTPase NRas [KO:K07828]
123788418  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
123776255  RRAS; ras-related protein R-Ras isoform X1 [KO:K07829]
123791661  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
123798360  E2F1; transcription factor E2F1 [KO:K17454]
123800588  HIF1A; hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
123794698  SP1; transcription factor Sp1 [KO:K04684]
123792132  TP53; cellular tumor antigen p53 [KO:K04451]
123798497  FOXO3; forkhead box protein O3 [KO:K09408]
123803359  CITED2; cbp/p300-interacting transactivator 2 [KO:K21361]
123799137  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
123779154  TFEB; transcription factor EB [KO:K15590]
123797175  TFE3; LOW QUALITY PROTEIN: transcription factor E3 [KO:K09105]
123784708  RABGEF1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
123788339  RAB5A; ras-related protein Rab-5A [KO:K07887]
123787269  RAB5B; ras-related protein Rab-5B [KO:K07888]
123781866  RAB5C; ras-related protein Rab-5C [KO:K07889]
123791324  MON1B; vacuolar fusion protein MON1 homolog B [KO:K20195]
123798677  MON1A; vacuolar fusion protein MON1 homolog A [KO:K20195]
123802527  CCZ1; vacuolar fusion protein CCZ1 homolog [KO:K27045]
123802067  RAB7A; ras-related protein Rab-7a [KO:K07897]
123785667  RAB7B; ras-related protein Rab-7b [KO:K07898]
123787121  TBC1D15; TBC1 domain family member 15 isoform X1 [KO:K20168]
123776238  TBC1D17; TBC1 domain family member 17 isoform X1 [KO:K19945]
123777283  FIS1; mitochondrial fission 1 protein [KO:K17969]
123788782  ATG9B; autophagy-related protein 9B [KO:K17907]
123779479  ATG9A; autophagy-related protein 9A isoform X1 [KO:K17907]
123802205  OPA1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
123781007  transitional endoplasmic reticulum ATPase [KO:K13525]
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
uar04140  Autophagy - animal
uar04210  Apoptosis
KO pathway
ko04137   
LinkDB

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