KEGG   PATHWAY: mcoc04137
Entry
mcoc04137                   Pathway                                
Name
Mitophagy - animal - Mastomys coucha (southern multimammate mouse)
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
mcoc04137  Mitophagy - animal
mcoc04137

Other DBs
GO: 0000422
Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116090484  Ambra1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
116096899  Pink1; serine/threonine-protein kinase PINK1, mitochondrial [KO:K05688] [EC:2.7.11.1]
116097534  mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
116103341  Tomm40l; mitochondrial import receptor subunit TOM40B [KO:K11518]
116101771  Tomm40; mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
116070442  Tomm20; mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
116080903  Tomm20l; TOMM20-like protein 1 [KO:K17770]
116086005  Tomm70; mitochondrial import receptor subunit TOM70 [KO:K17768]
116076805  Prkn; E3 ubiquitin-protein ligase parkin isoform X1 [KO:K04556] [EC:2.3.2.31]
116103789  Marchf5; E3 ubiquitin-protein ligase MARCH5 [KO:K10660] [EC:2.3.2.27]
116089826  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116068744  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
116077578  Smurf2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
116069886  Amfr; E3 ubiquitin-protein ligase AMFR isoform X1 [KO:K10636] [EC:2.3.2.36]
116096902  Mul1; mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
116089750  Huwe1; E3 ubiquitin-protein ligase HUWE1 isoform X1 [KO:K10592] [EC:2.3.2.26]
116069789  Siah1; E3 ubiquitin-protein ligase SIAH1 [KO:K04506] [EC:2.3.2.27]
116073498  Arih1; E3 ubiquitin-protein ligase ARIH1 isoform X1 [KO:K11968] [EC:2.3.2.31]
116095059  Mfn1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
116097001  Mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
116076739  Rhot1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
116076722  Rhot2; mitochondrial Rho GTPase 2 isoform X1 [KO:K07871] [EC:3.6.5.-]
116074216  ubiquitin-like [KO:K02927]
116069469  Uba52; ubiquitin-60S ribosomal protein L40 [KO:K02927]
116069335  Rps27a; ubiquitin-40S ribosomal protein S27a [KO:K02977]
116082443  LOW QUALITY PROTEIN: polyubiquitin-like [KO:K04551]
116087665  ubiquitin-like [KO:K04551]
116080143  ubiquitin [KO:K04551]
116098931  Tax1bp1; tax1-binding protein 1 [KO:K21347]
116077040  Sqstm1; sequestosome-1 isoform X1 [KO:K14381]
116077340  Calcoco2; calcium-binding and coiled-coil domain-containing protein 2 [KO:K21348]
116081709  Optn; optineurin isoform X1 [KO:K19946]
116078428  Nbr1; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
116076589  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
116099677  Gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
116077104  Gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
116070214  Gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
116070311  Map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
116091231  Map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
116077067  Becn1; beclin-1 isoform X1 [KO:K08334]
116071322  Becn2; beclin-2 [KO:K08334]
116091787  Usp8; ubiquitin carboxyl-terminal hydrolase 8 [KO:K11839] [EC:3.4.19.12]
116076276  Usp15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
116068213  Usp30; ubiquitin carboxyl-terminal hydrolase 30 isoform X1 [KO:K11851] [EC:3.4.19.12]
116091179  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
116068121  Pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
116069938  Csnk2a2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
116091160  Csnk2a1; casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
116074950  Csnk2b; casein kinase II subunit beta isoform X1 [KO:K03115]
116091289  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
116068139  Ulk1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
116072037  Fundc1; FUN14 domain-containing protein 1 [KO:K17986]
116103150  Bnip3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
116084492  Bnip3l; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like isoform X1 [KO:K15465]
116099517  Bcl2l13; bcl-2-like protein 13 isoform X1 [KO:K15485]
116069470  Fkbp8; peptidyl-prolyl cis-trans isomerase FKBP8 isoform X1 [KO:K09574] [EC:5.2.1.8]
116077066  Samm50; sorting and assembly machinery component 50 homolog [KO:K07277]
116099568  Phb2; prohibitin-2 [KO:K17081]
116073136  Nlrx1; NLR family member X1 [KO:K12653]
116083373  Mtx3; metaxin-3 isoform X1 [KO:K17776]
116093159  Mtx1; metaxin-1 [KO:K17776]
116090333  Mtx2; metaxin-2 isoform X1 [KO:K17776]
116099053  Eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
116080060  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
116076129  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
116085336  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116067982  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116076765  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116096245  Jun; transcription factor AP-1 [KO:K04448]
116103403  Rela; transcription factor p65 isoform X1 [KO:K04735]
116099791  Kras; GTPase KRas isoform X1 [KO:K07827]
116093530  Nras; GTPase NRas [KO:K07828]
116072312  Mras; ras-related protein M-Ras [KO:K07831]
116102164  Rras; ras-related protein R-Ras isoform X1 [KO:K07829]
116102825  Rras2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
116091213  E2f1; transcription factor E2F1 [KO:K17454]
116081194  Hif1a; hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
116080468  Sp1; transcription factor Sp1 isoform X1 [KO:K04684]
116077116  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
116075286  Foxo3; forkhead box protein O3 [KO:K09408]
116097792  Cited2; cbp/p300-interacting transactivator 2 [KO:K21361]
116099319  Mitf; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
116074538  Tfeb; transcription factor EB isoform X1 [KO:K15590]
116103044  Tfe3; transcription factor E3 isoform X1 [KO:K09105]
116068495  Rabgef1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
116074344  Rab5a; ras-related protein Rab-5A [KO:K07887]
116076052  Rab5b; ras-related protein Rab-5B [KO:K07888]
116102056  LOW QUALITY PROTEIN: ras-related protein Rab-5C-like [KO:K07889]
116078733  Rab5c; ras-related protein Rab-5C [KO:K07889]
116070224  Mon1b; vacuolar fusion protein MON1 homolog B isoform X1 [KO:K20195]
116073204  Mon1a; vacuolar fusion protein MON1 homolog A isoform X1 [KO:K20195]
116104701  Ccz1; vacuolar fusion protein CCZ1 homolog [KO:K27045]
116099215  Rab7a; ras-related protein Rab-7a [KO:K07897]
116098920  Rab7b; ras-related protein Rab-7b [KO:K07898]
116076554  Tbc1d15; TBC1 domain family member 15 [KO:K20168]
116102146  Tbc1d17; TBC1 domain family member 17 [KO:K19945]
116068570  Fis1; mitochondrial fission 1 protein [KO:K17969]
116097544  Atg9b; autophagy-related protein 9B [KO:K17907]
116088595  Atg9a; autophagy-related protein 9A isoform X1 [KO:K17907]
116085778  Opa1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
116095875  Vcp; transitional endoplasmic reticulum ATPase isoform X1 [KO:K13525]
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
mcoc04140  Autophagy - animal
mcoc04210  Apoptosis
KO pathway
ko04137   
LinkDB

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