KEGG   PATHWAY: hsa04137
Entry
hsa04137                    Pathway                                
Name
Mitophagy - animal - Homo sapiens (human)
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
hsa04137  Mitophagy - animal
hsa04137

Network
nt06463  Parkinson disease
nt06464  Amyotrophic lateral sclerosis
nt06466  Pathways of neurodegeneration
nt06536  Mitophagy
  Element
N01052  PINK1-Parkin-mediated MFN2 degradation
N01137  PINK-Parkin-mediated autophagosome formation
N01140  TBK1-mediated autophagosome formation
N01756  PINK-Parkin-independent ubiquitin-mediated mitophagy
N01757  PINK-Parkin-independent ubiquitin-mediated mitophagy, ubiquitin E3 ligase
N01759  INK1-Parkin-mediated MFN2 degradation, VCP-OPA1
N01760  Endosomal Rab cycles
Other DBs
GO: 0000422
Organism
Homo sapiens (human) [GN:hsa]
Gene
10075  HUWE1; HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 [KO:K10592] [EC:2.3.2.26]
10133  OPTN; optineurin [KO:K19946]
10241  CALCOCO2; calcium binding and coiled-coil domain 2 [KO:K21348]
10370  CITED2; Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2 [KO:K21361]
10452  TOMM40; translocase of outer mitochondrial membrane 40 [KO:K11518]
10651  MTX2; metaxin 2 [KO:K17776]
107986346  [KO:K17771]
11331  PHB2; prohibitin 2 [KO:K17081]
11337  GABARAP; GABA type A receptor-associated protein [KO:K08341]
11345  GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341]
139341  FUNDC1; FUN14 domain containing 1 [KO:K17986]
1457  CSNK2A1; casein kinase 2 alpha 1 [KO:K03097] [EC:2.7.11.1]
1459  CSNK2A2; casein kinase 2 alpha 2 [KO:K03097] [EC:2.7.11.1]
1460  CSNK2B; casein kinase 2 beta [KO:K03115]
1869  E2F1; E2F transcription factor 1 [KO:K17454]
192111  PGAM5; PGAM family member 5, mitochondrial serine/threonine protein phosphatase [KO:K15637] [EC:3.1.3.16]
1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
221960  CCZ1B; CCZ1 homolog B, vacuolar protein trafficking and biogenesis associated [KO:K27045]
22800  RRAS2; RAS related 2 [KO:K07830]
22808  MRAS; muscle RAS oncogene homolog [KO:K07831]
22879  MON1B; MON1 homolog B, secretory trafficking associated [KO:K20195]
2309  FOXO3; forkhead box O3 [KO:K09408]
23710  GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341]
23770  FKBP8; FKBP prolyl isomerase 8 [KO:K09574] [EC:5.2.1.8]
23786  BCL2L13; BCL2 like 13 [KO:K15485]
25813  SAMM50; SAMM50 sorting and assembly machinery component [KO:K07277]
25820  ARIH1; ariadne RBR E3 ubiquitin protein ligase 1 [KO:K11968] [EC:2.3.2.31]
267  AMFR; autocrine motility factor receptor [KO:K10636] [EC:2.3.2.36]
27342  RABGEF1; RAB guanine nucleotide exchange factor 1 [KO:K20131]
283106  CSNK2A3; casein kinase 2 alpha 3 [KO:K03097] [EC:2.7.11.1]
285973  ATG9B; autophagy related 9B [KO:K17907]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
3091  HIF1A; hypoxia inducible factor 1 subunit alpha [KO:K08268]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
338382  RAB7B; RAB7B, member RAS oncogene family [KO:K07898]
345778  MTX3; metaxin 3 [KO:K17776]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
387990  TOMM20L; translocase of outer mitochondrial membrane 20 like [KO:K17770]
392288  MAP1LC3BP1; microtubule associated protein 1 light chain 3 beta pseudogene 1 [KO:K10435]
4077  NBR1; NBR1 autophagy cargo receptor [KO:K17987]
4286  MITF; melanocyte inducing transcription factor [KO:K09455]
440738  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
441925  BECN2; beclin 2 [KO:K08334]
4580  MTX1; metaxin 1 [KO:K17776]
468  ATF4; activating transcription factor 4 [KO:K04374]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
4976  OPA1; OPA1 mitochondrial dynamin like GTPase [KO:K17079] [EC:3.6.5.5]
5071  PRKN; parkin RBR E3 ubiquitin protein ligase [KO:K04556] [EC:2.3.2.31]
51024  FIS1; fission, mitochondrial 1 [KO:K17969]
51622  CCZ1; CCZ1 homolog, vacuolar protein trafficking and biogenesis associated [KO:K27045]
54543  TOMM7; translocase of outer mitochondrial membrane 7 [KO:K17771]
54708  MARCHF5; membrane associated ring-CH-type finger 5 [KO:K10660] [EC:2.3.2.27]
55288  RHOT1; ras homolog family member T1 [KO:K07870] [EC:3.6.5.-]
55626  AMBRA1; autophagy and beclin 1 regulator 1 [KO:K17985]
55669  MFN1; mitofusin 1 [KO:K21356] [EC:3.6.5.-]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
57154  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
5868  RAB5A; RAB5A, member RAS oncogene family [KO:K07887]
5869  RAB5B; RAB5B, member RAS oncogene family [KO:K07888]
5878  RAB5C; RAB5C, member RAS oncogene family [KO:K07889]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
598  BCL2L1; BCL2 like 1 [KO:K04570]
6233  RPS27A; ribosomal protein S27a [KO:K02977]
6237  RRAS; RAS related [KO:K07829]
643246  MAP1LC3B2; microtubule associated protein 1 light chain 3 beta 2 [KO:K10435]
64750  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
6477  SIAH1; siah E3 ubiquitin protein ligase 1 [KO:K04506] [EC:2.3.2.27]
64786  TBC1D15; TBC1 domain family member 15 [KO:K20168]
65018  PINK1; PTEN induced kinase 1 [KO:K05688] [EC:2.7.11.1]
664  BNIP3; BCL2 interacting protein 3 [KO:K15464]
665  BNIP3L; BCL2 interacting protein 3 like [KO:K15465]
6667  SP1; Sp1 transcription factor [KO:K04684]
6714  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
7030  TFE3; transcription factor binding to IGHM enhancer 3 [KO:K09105]
7157  TP53; tumor protein p53 [KO:K04451]
7186  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
7311  UBA52; ubiquitin A-52 residue ribosomal protein fusion product 1 [KO:K02927]
7314  UBB; ubiquitin B [KO:K04551]
7316  UBC; ubiquitin C [KO:K08770]
7415  VCP; valosin containing protein [KO:K13525]
7879  RAB7A; RAB7A, member RAS oncogene family [KO:K07897]
79065  ATG9A; autophagy related 9A [KO:K17907]
7942  TFEB; transcription factor EB [KO:K15590]
79594  MUL1; mitochondrial E3 ubiquitin protein ligase 1 [KO:K15688] [EC:2.3.2.27]
79671  NLRX1; NLR family member X1 [KO:K12653]
79735  TBC1D17; TBC1 domain family member 17 [KO:K19945]
81631  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
8408  ULK1; unc-51 like autophagy activating kinase 1 [KO:K21357] [EC:2.7.11.1]
84134  TOMM40L; translocase of outer mitochondrial membrane 40 like [KO:K11518]
84315  MON1A; MON1 homolog A, secretory trafficking associated [KO:K20195]
84557  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
84749  USP30; ubiquitin specific peptidase 30 [KO:K11851] [EC:3.4.19.12]
8678  BECN1; beclin 1 [KO:K08334]
8878  SQSTM1; sequestosome 1 [KO:K14381]
8887  TAX1BP1; Tax1 binding protein 1 [KO:K21347]
89941  RHOT2; ras homolog family member T2 [KO:K07871] [EC:3.6.5.-]
9101  USP8; ubiquitin specific peptidase 8 [KO:K11839] [EC:3.4.19.12]
9451  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
9804  TOMM20; translocase of outer mitochondrial membrane 20 [KO:K17770]
9868  TOMM70; translocase of outer mitochondrial membrane 70 [KO:K17768]
9927  MFN2; mitofusin 2 [KO:K06030] [EC:3.6.5.-]
9958  USP15; ubiquitin specific peptidase 15 [KO:K21343] [EC:3.4.19.12]
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
hsa04140  Autophagy - animal
hsa04210  Apoptosis
KO pathway
ko04137   

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