KEGG   PATHWAY: ccan04137
Entry
ccan04137                   Pathway                                
Name
Mitophagy - animal - Castor canadensis (American beaver)
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
ccan04137  Mitophagy - animal
ccan04137

Other DBs
GO: 0000422
Organism
Castor canadensis (American beaver) [GN:ccan]
Gene
109674552  Gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
109674834  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
109676416  [KO:K17768]
109676686  Fkbp8; LOW QUALITY PROTEIN: peptidyl-prolyl cis-trans isomerase FKBP8 [KO:K09574] [EC:5.2.1.8]
109676707  Uba52; ubiquitin-60S ribosomal protein L40 isoform X1 [KO:K02927]
109677773  [KO:K02977]
109678159  [KO:K15485]
109681758  Rps27a; ubiquitin-40S ribosomal protein S27a [KO:K02977]
109682165  Tfeb; transcription factor EB [KO:K15590]
109682777  Phb2; prohibitin-2 [KO:K17081]
109682911  Hif1a; hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
109683325  Rhot1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
109683851  Rras; ras-related protein R-Ras isoform X1 [KO:K07829]
109683914  Tbc1d17; TBC1 domain family member 17 isoform X1 [KO:K19945]
109683965  Mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
109684019  Gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
109684073  Sp1; transcription factor Sp1 [KO:K04684]
109684429  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
109685307  Vcp; transitional endoplasmic reticulum ATPase isoform X1 [KO:K13525]
109685569  Mon1b; vacuolar fusion protein MON1 homolog B isoform X1 [KO:K20195]
109685898  Map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
109685925  Rabgef1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
109686271  Pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial [KO:K15637] [EC:3.1.3.16]
109686728  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
109686732  Sqstm1; sequestosome-1 isoform X1 [KO:K14381]
109686738  [KO:K04440] [EC:2.7.11.24]
109687013  Csnk2a2; casein kinase II subunit alpha' [KO:K03097] [EC:2.7.11.1]
109687015  Csnk2a1; casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
109687060  Kras; GTPase KRas [KO:K07827]
109687142  Rela; transcription factor p65 isoform X1 [KO:K04735]
109687340  Becn1; beclin-1 isoform X1 [KO:K08334]
109687349  Nbr1; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
109688024  Mtx1; metaxin-1 [KO:K17776]
109688027  March5; E3 ubiquitin-protein ligase MARCH5 [KO:K10660] [EC:2.3.2.27]
109688031  [KO:K04556] [EC:2.3.2.31]
109688416  Arih1; E3 ubiquitin-protein ligase ARIH1 [KO:K11968] [EC:2.3.2.31]
109689665  Mfn1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
109689684  Mul1; mitochondrial ubiquitin ligase activator of NFKB 1 isoform X1 [KO:K15688] [EC:2.3.2.27]
109689686  Pink1; serine/threonine-protein kinase PINK1, mitochondrial [KO:K05688] [EC:2.7.11.1]
109689711  Gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
109690083  [KO:K19946]
109690547  Usp30; ubiquitin carboxyl-terminal hydrolase 30 [KO:K11851] [EC:3.4.19.12]
109690765  E2f1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
109691072  Atg9a; autophagy-related protein 9A [KO:K17907]
109691371  Mitf; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
109691766  Bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
109692005  Ambra1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
109692310  Ubb; LOW QUALITY PROTEIN: polyubiquitin-B [KO:K04551]
109692403  Tomm40; mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
109692624  Tomm20; mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
109692646  Rab5a; ras-related protein Rab-5A [KO:K07887]
109692690  Mon1a; vacuolar fusion protein MON1 homolog A [KO:K20195]
109692812  Fis1; mitochondrial fission 1 protein [KO:K17969]
109692912  Ccz1; vacuolar fusion protein CCZ1 homolog [KO:K27045]
109692964  Calcoco2; calcium-binding and coiled-coil domain-containing protein 2 isoform X1 [KO:K21348]
109693025  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109693121  Samm50; sorting and assembly machinery component 50 homolog [KO:K07277]
109693210  Tomm40l; LOW QUALITY PROTEIN: mitochondrial import receptor subunit TOM40B [KO:K11518]
109693271  Cited2; cbp/p300-interacting transactivator 2 [KO:K21361]
109693328  [KO:K04506] [EC:2.3.2.27]
109693432  Becn2; beclin-2 [KO:K08334]
109693559  Mras; ras-related protein M-Ras [KO:K07831]
109693603  Usp15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
109694062  Bnip3l; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like [KO:K15465]
109694436  Atg9b; LOW QUALITY PROTEIN: autophagy-related protein 9B [KO:K17907]
109694572  Csnk2b; casein kinase II subunit beta [KO:K03115]
109694920  Rhot2; mitochondrial Rho GTPase 2 isoform X1 [KO:K07871] [EC:3.6.5.-]
109695045  Mtx2; metaxin-2 isoform X1 [KO:K17776]
109695377  Tbc1d15; TBC1 domain family member 15 isoform X1 [KO:K20168]
109695442  Rras2; ras-related protein R-Ras2 [KO:K07830]
109695587  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
109695774  Rab5c; ras-related protein Rab-5C [KO:K07889]
109695795  Huwe1; E3 ubiquitin-protein ligase HUWE1 isoform X1 [KO:K10592] [EC:2.3.2.26]
109696062  Nras; GTPase NRas [KO:K07828]
109696215  Nlrx1; NLR family member X1 [KO:K12653]
109696466  Map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
109696482  Rab7a; ras-related protein Rab-7a [KO:K07897]
109696790  Tax1bp1; LOW QUALITY PROTEIN: tax1-binding protein 1 [KO:K21347]
109697223  Rab7b; ras-related protein Rab-7b [KO:K07898]
109697545  Ulk1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
109697813  Siah1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
109697831  Opa1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
109698042  Hras; GTPase HRas isoform X1 [KO:K02833]
109698137  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
109698573  Rab5b; ras-related protein Rab-5B [KO:K07888]
109698630  Bnip3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
109699331  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
109699492  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
109699634  [KO:K17986]
109699888  Tfe3; transcription factor E3 isoform X1 [KO:K09105]
109700070  Tomm20l; TOMM20-like protein 1 [KO:K17770]
109700276  Usp8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
109700415  Amfr; E3 ubiquitin-protein ligase AMFR [KO:K10636] [EC:2.3.2.36]
109700514  Ubc; LOW QUALITY PROTEIN: polyubiquitin-C [KO:K08770]
109700588  Mtx3; metaxin-3 isoform X1 [KO:K17776]
109700754  Foxo3; forkhead box protein O3 [KO:K09408]
109700777  Jun; transcription factor AP-1 [KO:K04448]
109701043  Tomm7; mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
109702281  [KO:K05704] [EC:2.7.10.2]
109703004  [KO:K04440] [EC:2.7.11.24]
109703335  [KO:K07887]
Compound
C00035  GDP
C00044  GTP
Reference
PMID:25611507
  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
PMID:25995186
  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
PMID:25999423
  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
PMID:26611876
  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
PMID:26882551
  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
PMID:27021519
  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
PMID:27443527
  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
PMID:27701735
  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
ccan04140  Autophagy - animal
ccan04210  Apoptosis
KO pathway
ko04137   

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