KEGG   PATHWAY: muo04137
Entry
muo04137                    Pathway                                
Name
Mitophagy - animal - Microcaecilia unicolor
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
muo04137  Mitophagy - animal
muo04137

Other DBs
GO: 0000422
Organism
Microcaecilia unicolor [GN:muo]
Gene
115468831  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985]
115460119  TOMM7; mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
115475564  TOMM40; mitochondrial import receptor subunit TOM40 homolog isoform X1 [KO:K11518]
115458061  TOMM40L; mitochondrial import receptor subunit TOM40B [KO:K11518]
115466675  TOMM20; mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
115470683  TOMM70; mitochondrial import receptor subunit TOM70 [KO:K17768]
115469229  E3 ubiquitin-protein ligase MARCH5-like [KO:K10660] [EC:2.3.2.27]
115470102  MARCHF5; E3 ubiquitin-protein ligase MARCH5 [KO:K10660] [EC:2.3.2.27]
115472619  TRAF2; LOW QUALITY PROTEIN: TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
115475366  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
115472575  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
115470492  AMFR; E3 ubiquitin-protein ligase AMFR isoform X1 [KO:K10636] [EC:2.3.2.36]
115456642  MUL1; mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
115463600  HUWE1; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase HUWE1 [KO:K10592] [EC:2.3.2.26]
115470813  SIAH1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
115457913  ARIH1; E3 ubiquitin-protein ligase ARIH1 isoform X1 [KO:K11968] [EC:2.3.2.31]
115479131  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
115482486  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
115473447  RHOT1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
115476066  RHOT2; mitochondrial Rho GTPase 2 [KO:K07871] [EC:3.6.5.-]
115479825  UBA52; ubiquitin-60S ribosomal protein L40 [KO:K02927]
115462898  ubiquitin-40S ribosomal protein S27a [KO:K02977]
115465750  ubiquitin-40S ribosomal protein S27a-like [KO:K02977]
115481113  UBC; polyubiquitin-C [KO:K08770]
115482554  polyubiquitin-C-like [KO:K08770]
115482555  polyubiquitin-C [KO:K08770]
115469671  TAX1BP1; LOW QUALITY PROTEIN: tax1-binding protein 1 [KO:K21347]
115476938  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
115458800  sequestosome-1-like isoform X1 [KO:K14381]
115482031  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 isoform X1 [KO:K21348]
115478430  OPTN; optineurin [KO:K19946]
115481349  LOW QUALITY PROTEIN: next to BRCA1 gene 1 protein-like [KO:K17987]
115481352  next to BRCA1 gene 1 protein-like isoform X1 [KO:K17987]
115479322  TBK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
115471012  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
115457775  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
115458372  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
115458892  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
115480577  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
115475705  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
115464850  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
115470930  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
115481969  BECN1; beclin-1 [KO:K08334]
115459811  USP8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
115479357  USP15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
115480512  USP30; ubiquitin carboxyl-terminal hydrolase 30 [KO:K11851] [EC:3.4.19.12]
115476548  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
115459534  bcl-2-like protein 1 isoform X1 [KO:K04570]
115479641  PGAM5; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PGAM5, mitochondrial [KO:K15637] [EC:3.1.3.16]
115481564  casein kinase II subunit alpha-like isoform X1 [KO:K03097] [EC:2.7.11.1]
115475718  CSNK2A1; LOW QUALITY PROTEIN: casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
115470413  CSNK2A2; casein kinase II subunit alpha' [KO:K03097] [EC:2.7.11.1]
115466306  CSNK2B; casein kinase II subunit beta [KO:K03115]
115477002  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
115479510  ULK1; serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
115474077  FUNDC2; FUN14 domain-containing protein 2 isoform X1 [KO:K17986]
115468159  FUNDC1; FUN14 domain-containing protein 1 [KO:K17986]
115462541  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like [KO:K15464]
115470079  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
115458945  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like [KO:K15464]
115469324  BNIP3L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like isoform X1 [KO:K15465]
115477955  BCL2L13; bcl-2-like protein 13 [KO:K15485]
115479822  FKBP8; peptidyl-prolyl cis-trans isomerase FKBP8 [KO:K09574] [EC:5.2.1.8]
115477884  SAMM50; sorting and assembly machinery component 50 homolog isoform X1 [KO:K07277]
115457868  PHB2; prohibitin-2 [KO:K17081]
115482315  NLRX1; NLR family member X1 [KO:K12653]
115473989  MTX2; metaxin-2 [KO:K17776]
115463041  MTX3; metaxin-3 isoform X1 [KO:K17776]
115458294  MTX1; metaxin-1 isoform X1 [KO:K17776]
115461322  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
115477226  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
115473430  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
115461062  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
115476478  MAPK9; LOW QUALITY PROTEIN: mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
115470198  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
115472249  JUN; transcription factor AP-1 [KO:K04448]
115480195  RELA; LOW QUALITY PROTEIN: transcription factor p65 [KO:K04735]
115469027  HRAS; GTPase HRas [KO:K02833]
115477562  KRAS; GTPase KRas isoform X1 [KO:K07827]
115466597  GTPase HRas-like [KO:K07827]
115481569  NRAS; GTPase NRas [KO:K07828]
115474038  ras-related protein M-Ras isoform X1 [KO:K07831]
115474773  ras-related protein M-Ras [KO:K07831]
115468902  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
115465031  RRAS; ras-related protein R-Ras [KO:K07830]
115476036  E2F1; transcription factor E2F1 [KO:K17454]
115477341  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
115466821  SP1; transcription factor Sp1 [KO:K04684]
115457986  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
115467315  FOXO3; LOW QUALITY PROTEIN: forkhead box protein O3 [KO:K09408]
115466944  CITED2; cbp/p300-interacting transactivator 2 [KO:K21361]
115473516  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
115481550  TFEB; transcription factor EB [KO:K15590]
115463469  TFE3; transcription factor E3 isoform X1 [KO:K09105]
115480834  LOW QUALITY PROTEIN: rab5 GDP/GTP exchange factor-like [KO:K20131]
115456519  RABGEF1; rab5 GDP/GTP exchange factor [KO:K20131]
115459304  rab5 GDP/GTP exchange factor-like [KO:K20131]
115469933  RAB5A; ras-related protein Rab-5A [KO:K07887]
115474191  ras-related protein Rab-5B-like isoform X1 [KO:K07888]
115465901  RAB5B; ras-related protein Rab-5B [KO:K07888]
115481635  RAB5C; ras-related protein Rab-5C [KO:K07889]
115463458  vacuolar fusion protein MON1 homolog B-like isoform X1 [KO:K20195]
115471661  MON1A; vacuolar fusion protein MON1 homolog A isoform X1 [KO:K20195]
115476434  CCZ1; vacuolar fusion protein CCZ1 homolog [KO:K27045]
115471578  RAB7A; ras-related protein Rab-7a [KO:K07897]
115482109  RAB7B; ras-related protein Rab-7b [KO:K07898]
115477438  TBC1D15; TBC1 domain family member 15 [KO:K20168]
115466624  TBC1D17; TBC1 domain family member 17 isoform X1 [KO:K19945]
115457515  mitochondrial fission 1 protein-like isoform X1 [KO:K17969]
115474525  ATG9A; autophagy-related protein 9A isoform X1 [KO:K17907]
115465200  ATG9B; autophagy-related protein 9B [KO:K17907]
115479301  OPA1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
115461786  transitional endoplasmic reticulum ATPase-like [KO:K13525]
115462810  VCP; transitional endoplasmic reticulum ATPase [KO:K13525]
115466101  transitional endoplasmic reticulum ATPase-like [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
muo04140  Autophagy - animal
muo04210  Apoptosis
KO pathway
ko04137   
LinkDB

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