KEGG   PATHWAY: elk04137
Entry
elk04137                    Pathway                                
Name
Mitophagy - animal - Enhydra lutris kenyoni (northern sea otter)
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
elk04137  Mitophagy - animal
elk04137

Other DBs
GO: 0000422
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111149427  activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
111154572  serine/threonine-protein kinase PINK1, mitochondrial [KO:K05688] [EC:2.7.11.1]
111147415  mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
111160709  mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
111138901  mitochondrial import receptor subunit TOM40B isoform X1 [KO:K11518]
111161462  TOMM20-like protein 1 [KO:K17770]
111160491  mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
111151676  mitochondrial import receptor subunit TOM70 [KO:K17768]
111158711  E3 ubiquitin-protein ligase parkin [KO:K04556] [EC:2.3.2.31]
111145015  E3 ubiquitin-protein ligase MARCH5 [KO:K10660] [EC:2.3.2.27]
111145476  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
111146100  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
111145504  E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
111158164  E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
111157345  E3 ubiquitin-protein ligase AMFR [KO:K10636] [EC:2.3.2.36]
111154701  mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
111139808  E3 ubiquitin-protein ligase HUWE1 isoform X1 [KO:K10592] [EC:2.3.2.26]
111157148  E3 ubiquitin-protein ligase SIAH1-like [KO:K04506] [EC:2.3.2.27]
111157325  E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
111153169  E3 ubiquitin-protein ligase ARIH1 [KO:K11968] [EC:2.3.2.31]
111148243  mitofusin-1 [KO:K21356] [EC:3.6.5.-]
111154723  mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
111151308  mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
111156193  mitochondrial Rho GTPase 2 isoform X1 [KO:K07871] [EC:3.6.5.-]
111154816  ubiquitin-60S ribosomal protein L40-like [KO:K02927]
111148280  ubiquitin-like isoform X1 [KO:K02927]
111143805  ubiquitin-60S ribosomal protein L40 isoform X1 [KO:K02927]
111141316  ubiquitin-60S ribosomal protein L40-like isoform X1 [KO:K02927]
111148109  ubiquitin-40S ribosomal protein S27a [KO:K02977]
111139471  LOW QUALITY PROTEIN: polyubiquitin-B [KO:K04551]
111147232  tax1-binding protein 1 isoform X1 [KO:K21347]
111158853  sequestosome-1 [KO:K14381]
111151555  calcium-binding and coiled-coil domain-containing protein 2 isoform X1 [KO:K21348]
111155530  optineurin isoform X1 [KO:K19946]
111151636  next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
111142106  serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
111152932  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
111161123  gamma-aminobutyric acid receptor-associated protein isoform X1 [KO:K08341]
111142199  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
111150637  microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
111152982  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
111141551  microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
111150658  beclin-2 [KO:K08334]
111151520  beclin-1 isoform X1 [KO:K08334]
111160514  ubiquitin carboxyl-terminal hydrolase 8 [KO:K11839] [EC:3.4.19.12]
111160148  ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
111156369  ubiquitin carboxyl-terminal hydrolase 30 isoform X1 [KO:K11851] [EC:3.4.19.12]
111141775  bcl-2-like protein 1 [KO:K04570]
111139781  serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
111141414  casein kinase II subunit alpha isoform X1 [KO:K03097] [EC:2.7.11.1]
111157353  casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
111152166  casein kinase II subunit beta isoform X1 [KO:K03115]
111141563  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
111140006  serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
111144272  FUN14 domain-containing protein 1-like [KO:K17986]
111150502  FUN14 domain-containing protein 1 [KO:K17986]
111144888  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
111154216  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like isoform X1 [KO:K15465]
111159728  bcl-2-like protein 13 isoform X1 [KO:K15485]
111143795  peptidyl-prolyl cis-trans isomerase FKBP8 isoform X1 [KO:K09574] [EC:5.2.1.8]
111157610  sorting and assembly machinery component 50 homolog [KO:K07277]
111159816  prohibitin-2 isoform X1 [KO:K17081]
111140569  prohibitin-2-like [KO:K17081]
111153942  NLR family member X1 isoform X1 [KO:K12653]
111144877  metaxin-2 isoform X1 [KO:K17776]
111148278  metaxin-3 [KO:K17776]
111138894  metaxin-1 isoform X1 [KO:K17776]
111148064  eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
111148773  eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
111157635  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
111144860  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
111158897  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111154016  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111143174  transcription factor AP-1 [KO:K04448]
111149956  transcription factor p65 [KO:K04735]
111140316  GTPase HRas isoform X1 [KO:K02833]
111159984  GTPase KRas isoform X1 [KO:K07827]
111143238  GTPase NRas [KO:K07828]
111155011  ras-related protein M-Ras [KO:K07831]
111160680  ras-related protein R-Ras [KO:K07829]
111159398  ras-related protein R-Ras2 isoform X1 [KO:K07830]
111141556  transcription factor E2F1 [KO:K17454]
111159390  hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
111157856  transcription factor Sp1 isoform X1 [KO:K04684]
111161133  cellular tumor antigen p53 [KO:K04451]
111158279  forkhead box protein O3 [KO:K09408]
111147852  cbp/p300-interacting transactivator 2 [KO:K21361]
111143979  microphthalmia-associated transcription factor isoform X1 [KO:K09455]
111147504  transcription factor EB isoform X1 [KO:K15590]
111150460  transcription factor E3 [KO:K09105]
111145654  rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
111155079  ras-related protein Rab-5A [KO:K07887]
111160136  ras-related protein Rab-5B isoform X1 [KO:K07888]
111143471  ras-related protein Rab-5B-like isoform X1 [KO:K07888]
111151692  ras-related protein Rab-5C [KO:K07889]
111144318  vacuolar fusion protein MON1 homolog A isoform X1 [KO:K20195]
111152964  vacuolar fusion protein MON1 homolog B isoform X1 [KO:K20195]
111145627  vacuolar fusion protein CCZ1 homolog [KO:K27045]
111158993  ras-related protein Rab-7a isoform X1 [KO:K07897]
111151164  ras-related protein Rab-7b isoform X1 [KO:K07898]
111142123  TBC1 domain family member 15 isoform X1 [KO:K20168]
111160541  TBC1 domain family member 17 isoform X1 [KO:K19945]
111145576  mitochondrial fission 1 protein isoform X1 [KO:K17969]
111150832  autophagy-related protein 9A isoform X1 [KO:K17907]
111154535  autophagy-related protein 9B [KO:K17907]
111155040  dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
111145449  transitional endoplasmic reticulum ATPase isoform X1 [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
elk04140  Autophagy - animal
elk04210  Apoptosis
KO pathway
ko04137   
LinkDB

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