KEGG   PATHWAY: ppad04137
Entry
ppad04137                   Pathway                                
Name
Mitophagy - animal - Panthera pardus (leopard)
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
ppad04137  Mitophagy - animal
ppad04137

Other DBs
GO: 0000422
Organism
Panthera pardus (leopard) [GN:ppad]
Gene
109245100  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 [KO:K17985]
109274247  PINK1; serine/threonine-protein kinase PINK1, mitochondrial isoform X1 [KO:K05688] [EC:2.7.11.1]
109263817  TOMM7; mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
109257292  TOMM40L; mitochondrial import receptor subunit TOM40B isoform X1 [KO:K11518]
109253258  TOMM40; mitochondrial import receptor subunit TOM40 homolog isoform X1 [KO:K11518]
109268408  TOMM20L; TOMM20-like protein 1 [KO:K17770]
109248885  TOMM20; mitochondrial import receptor subunit TOM20 homolog isoform X1 [KO:K17770]
109266313  TOMM70; mitochondrial import receptor subunit TOM70 [KO:K17768]
109245483  PARK2; E3 ubiquitin-protein ligase parkin isoform X1 [KO:K04556] [EC:2.3.2.31]
109264655  MARCH5; E3 ubiquitin-protein ligase MARCH5 [KO:K10660] [EC:2.3.2.27]
109258781  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
109251227  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
109277076  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
109270896  AMFR; E3 ubiquitin-protein ligase AMFR [KO:K10636] [EC:2.3.2.36]
109274243  MUL1; mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
109260273  HUWE1; E3 ubiquitin-protein ligase HUWE1 isoform X1 [KO:K10592] [EC:2.3.2.26]
109248333  E3 ubiquitin-protein ligase SIAH1-like [KO:K04506] [EC:2.3.2.27]
109270972  SIAH1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
109262729  ARIH1; E3 ubiquitin-protein ligase ARIH1 [KO:K11968] [EC:2.3.2.31]
109275163  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
109274124  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
109251902  RHOT1; mitochondrial Rho GTPase 1 isoform X1 [KO:K07870] [EC:3.6.5.-]
109259635  RHOT2; mitochondrial Rho GTPase 2 isoform X1 [KO:K07871] [EC:3.6.5.-]
109247632  UBA52; ubiquitin-60S ribosomal protein L40 [KO:K02927]
109252147  RPS27A; ubiquitin-40S ribosomal protein S27a [KO:K02977]
109255456  ubiquitin-40S ribosomal protein S27a-like [KO:K02977]
109245820  UBB; polyubiquitin-B [KO:K04551]
109263887  TAX1BP1; tax1-binding protein 1 isoform X1 [KO:K21347]
109278963  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
109247339  CALCOCO2; calcium-binding and coiled-coil domain-containing protein 2 isoform X1 [KO:K21348]
109273718  OPTN; optineurin isoform X1 [KO:K19946]
109258508  NBR1; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
109270431  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
109245686  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
109259070  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
109245976  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
109251424  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
109245565  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
109250512  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
109272536  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
109258570  BECN1; beclin-1 isoform X1 [KO:K08334]
109250249  BECN2; beclin-2 [KO:K08334]
109262999  USP8; ubiquitin carboxyl-terminal hydrolase 8 [KO:K11839] [EC:3.4.19.12]
109270408  USP15; ubiquitin carboxyl-terminal hydrolase 15 isoform X1 [KO:K21343] [EC:3.4.19.12]
109277480  USP30; ubiquitin carboxyl-terminal hydrolase 30 isoform X1 [KO:K11851] [EC:3.4.19.12]
109272592  BCL2L1; bcl-2-like protein 1 [KO:K04570]
109260670  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
109272621  CSNK2A1; casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
109270846  CSNK2A2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:2.7.11.1]
109260518  CSNK2B; casein kinase II subunit beta [KO:K03115]
109272472  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
109260065  ULK1; serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
109248050  FUNDC1; FUN14 domain-containing protein 1 isoform X1 [KO:K17986]
109256722  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
109277308  BNIP3L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like isoform X1 [KO:K15465]
109276275  BCL2L13; bcl-2-like protein 13 isoform X1 [KO:K15485]
109247630  FKBP8; peptidyl-prolyl cis-trans isomerase FKBP8 isoform X1 [KO:K09574] [EC:5.2.1.8]
109265690  SAMM50; sorting and assembly machinery component 50 homolog [KO:K07277]
109276091  PHB2; prohibitin-2 isoform X1 [KO:K17081]
109276092  prohibitin-2 [KO:K17081]
109278526  NLRX1; NLR family member X1 [KO:K12653]
109273518  MTX2; metaxin-2 [KO:K17776]
109256254  MTX1; LOW QUALITY PROTEIN: metaxin-1 [KO:K17776]
109274930  metaxin-3 isoform X1 [KO:K17776]
109274931  metaxin-3-like isoform X1 [KO:K17776]
109268294  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
109265586  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109278973  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
109276314  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
109264550  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109266785  JUN; transcription factor AP-1 [KO:K04448]
109246747  RELA; transcription factor p65 isoform X1 [KO:K04735]
109259759  GTPase HRas [KO:K02833]
109268745  KRAS; GTPase KRas isoform X1 [KO:K07827]
109272105  NRAS; GTPase NRas [KO:K07828]
109259803  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
109252867  RRAS; LOW QUALITY PROTEIN: ras-related protein R-Ras [KO:K07829]
109271166  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
109272548  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
109268360  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
109249199  SP1; transcription factor Sp1 [KO:K04684]
109245932  TP53; cellular tumor antigen p53 [KO:K04451]
109263506  FOXO3; forkhead box protein O3 [KO:K09408]
109249848  CITED2; cbp/p300-interacting transactivator 2 [KO:K21361]
109254484  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
109271602  TFEB; transcription factor EB isoform X1 [KO:K15590]
109248086  TFE3; transcription factor E3 isoform X1 [KO:K09105]
109250648  RABGEF1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
109258513  RAB5A; ras-related protein Rab-5A isoform X1 [KO:K07887]
109270310  RAB5B; ras-related protein Rab-5B [KO:K07888]
109258524  RAB5C; ras-related protein Rab-5C [KO:K07889]
109247827  MON1A; vacuolar fusion protein MON1 homolog A isoform X1 [KO:K20195]
109245674  MON1B; vacuolar fusion protein MON1 homolog B [KO:K20195]
109251206  CCZ1; vacuolar fusion protein CCZ1 homolog [KO:K27045]
109256040  RAB7A; ras-related protein Rab-7a [KO:K07897]
109257543  RAB7B; ras-related protein Rab-7b isoform X1 [KO:K07898]
109270519  TBC1D15; TBC1 domain family member 15 isoform X1 [KO:K20168]
109253033  TBC1D17; TBC1 domain family member 17 isoform X1 [KO:K19945]
109250539  FIS1; mitochondrial fission 1 protein [KO:K17969]
109252367  ATG9B; autophagy-related protein 9B isoform X1 [KO:K17907]
109265029  ATG9A; autophagy-related protein 9A [KO:K17907]
109266590  OPA1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
109270188  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
ppad04140  Autophagy - animal
ppad04210  Apoptosis
KO pathway
ko04137   
LinkDB

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