KEGG   PATHWAY: mcf04137
Entry
mcf04137                    Pathway                                
Name
Mitophagy - animal - Macaca fascicularis (crab-eating macaque)
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
mcf04137  Mitophagy - animal
mcf04137

Other DBs
GO: 0000422
Organism
Macaca fascicularis (crab-eating macaque) [GN:mcf]
Gene
101925989  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
102125675  PINK1; serine/threonine-protein kinase PINK1, mitochondrial [KO:K05688] [EC:2.7.11.1]
102138596  TOMM7; mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
102138102  TOMM40; mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
101925730  TOMM40L; mitochondrial import receptor subunit TOM40B isoform X1 [KO:K11518]
102137021  TOMM20L; TOMM20-like protein 1 [KO:K17770]
102119508  TOMM20; mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
102137706  TOMM70; mitochondrial import receptor subunit TOM70 [KO:K17768]
102134446  PRKN; E3 ubiquitin-protein ligase parkin isoform X1 [KO:K04556] [EC:2.3.2.31]
102126725  MARCHF5; E3 ubiquitin-protein ligase MARCHF5 [KO:K10660] [EC:2.3.2.27]
101925175  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
102126087  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
102123469  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
101865016  AMFR; E3 ubiquitin-protein ligase AMFR [KO:K10636] [EC:2.3.2.36]
101864962  MUL1; mitochondrial ubiquitin ligase activator of NFKB 1 isoform X1 [KO:K15688] [EC:2.3.2.27]
101925279  HUWE1; E3 ubiquitin-protein ligase HUWE1 isoform X10 [KO:K10592] [EC:2.3.2.26]
102147140  E3 ubiquitin-protein ligase SIAH1-like [KO:K04506] [EC:2.3.2.27]
102143770  SIAH1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
102119270  ARIH1; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase ARIH1 [KO:K11968] [EC:2.3.2.31]
102124269  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
101926564  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
101926801  RHOT1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
102118818  RHOT2; mitochondrial Rho GTPase 2 isoform X3 [KO:K07871] [EC:3.6.5.-]
102117118  ubiquitin-like [KO:K02927]
102115834  ubiquitin-like [KO:K02927]
101866252  UBA52; ubiquitin-60S ribosomal protein L40 isoform X2 [KO:K02927]
102136294  ubiquitin-60S ribosomal protein L40-like [KO:K02927]
102142514  RPS27A; ubiquitin-40S ribosomal protein S27a [KO:K02977]
101864869  ubiquitin-40S ribosomal protein S27a [KO:K02977]
102146874  ubiquitin-40S ribosomal protein S27a-like [KO:K02977]
102141400  ubiquitin-40S ribosomal protein S27a-like [KO:K02977]
102123991  ubiquitin-40S ribosomal protein S27a-like [KO:K02977]
101926775  UBB; polyubiquitin-B [KO:K04551]
102143130  UBC; polyubiquitin-C [KO:K08770]
101925628  TAX1BP1; tax1-binding protein 1 isoform X1 [KO:K21347]
102144942  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
101865725  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 isoform X1 [KO:K21348]
102122718  OPTN; optineurin isoform X3 [KO:K19946]
102118025  NBR1; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
102144774  TBK1; serine/threonine-protein kinase TBK1 isoform X2 [KO:K05410] [EC:2.7.11.10]
102145217  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
101925587  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X2 [KO:K08341]
101864971  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
102122168  gamma-aminobutyric acid receptor-associated protein-like [KO:K08341]
101926715  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A isoform X2 [KO:K10435]
102147181  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
101925226  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B isoform X2 [KO:K10435]
102146106  microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
102133082  microtubule-associated proteins 1A/1B light chain 3B-like [KO:K10435]
102115402  BECN2; beclin-2 [KO:K08334]
101867267  BECN1; beclin-1 isoform X1 [KO:K08334]
101926489  USP8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
101865179  USP15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
101864868  USP30; ubiquitin carboxyl-terminal hydrolase 30 isoform X1 [KO:K11851] [EC:3.4.19.12]
102140222  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
102128936  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
102125825  CSNK2A1; casein kinase II subunit alpha isoform X1 [KO:K03097] [EC:2.7.11.1]
101865560  CSNK2A2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
102125227  CSNK2B; casein kinase II subunit beta [KO:K03115]
102116225  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102141167  ULK1; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
102119471  FUNDC1; FUN14 domain-containing protein 1 isoform X2 [KO:K17986]
123574090  FUN14 domain-containing protein 1-like [KO:K17986]
102116967  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
102122068  BNIP3L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like [KO:K15465]
101866359  BCL2L13; bcl-2-like protein 13 isoform X1 [KO:K15485]
101864844  FKBP8; peptidyl-prolyl cis-trans isomerase FKBP8 isoform X3 [KO:K09574] [EC:5.2.1.8]
101864914  SAMM50; sorting and assembly machinery component 50 homolog [KO:K07277]
102136314  PHB2; prohibitin-2 [KO:K17081]
102134229  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
102127144  MTX3; metaxin-3 isoform X3 [KO:K17776]
102131884  MTX2; metaxin-2 isoform X2 [KO:K17776]
101926624  MTX1; metaxin-1 [KO:K17776]
123571778  metaxin-1-like [KO:K17776]
102117377  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
101925386  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
102117938  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102118497  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126339  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102121272  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126446  JUN; transcription factor AP-1 [KO:K04448]
101867324  RELA; transcription factor p65 isoform X1 [KO:K04735]
102118744  HRAS; GTPase HRas isoform X1 [KO:K02833]
102131483  KRAS; GTPase KRas isoform X1 [KO:K07827]
102137913  NRAS; GTPase NRas [KO:K07828]
101865297  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
102131991  RRAS; ras-related protein R-Ras [KO:K07829]
102143296  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
102146018  E2F1; transcription factor E2F1 [KO:K17454]
101866092  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
102115996  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
102135998  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
101925779  FOXO3; forkhead box protein O3 [KO:K09408]
102126995  CITED2; cbp/p300-interacting transactivator 2 [KO:K21361]
102121325  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
102125485  TFEB; transcription factor EB isoform X2 [KO:K15590]
102144652  TFE3; transcription factor E3 [KO:K09105]
102135775  RABGEF1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
102144117  RAB5A; ras-related protein Rab-5A [KO:K07887]
101865961  RAB5B; ras-related protein Rab-5B [KO:K07888]
102116190  RAB5C; ras-related protein Rab-5C [KO:K07889]
102133230  ras-related protein Rab-5C-like [KO:K07889]
101866652  MON1B; vacuolar fusion protein MON1 homolog B isoform X1 [KO:K20195]
102126726  MON1A; vacuolar fusion protein MON1 homolog A isoform X2 [KO:K20195]
102116774  vacuolar fusion protein CCZ1 homolog B isoform X1 [KO:K27045]
102143515  RAB7A; ras-related protein Rab-7a [KO:K07897]
102137760  RAB7B; ras-related protein Rab-7b isoform X4 [KO:K07898]
101865877  TBC1D15; TBC1 domain family member 15 isoform X1 [KO:K20168]
102138972  TBC1D17; TBC1 domain family member 17 isoform X1 [KO:K19945]
107126408  FIS1; mitochondrial fission 1 protein isoform X2 [KO:K17969]
102145270  ATG9B; autophagy-related protein 9B [KO:K17907]
102143533  ATG9A; autophagy-related protein 9A isoform X1 [KO:K17907]
102117668  OPA1; dynamin-like 120 kDa protein, mitochondrial isoform X5 [KO:K17079] [EC:3.6.5.5]
101864872  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
mcf04140  Autophagy - animal
mcf04210  Apoptosis
KO pathway
ko04137   
LinkDB

DBGET integrated database retrieval system